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Starting Dose (starting + dose)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Transplantation	13%
Neurology	10%
Pain Medicine	6%
13 Other Subdomains	55%

Selected Abstracts

ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse Attempt

THE JOURNAL OF SEXUAL MEDICINE, Issue 10 2009
Oleg B. Loran MD
ABSTRACT Introduction., Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. Aim., Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. Methods., Men with ED (score ,25 on the Erectile Function domain of the International Index of Erectile Function) who had received ,6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg). Main Outcome Measures., Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. Results., Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. Conclusions., Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose. Loran OB, Ströberg P, Lee SW, Park NC, Kim SW, Tseng LJ, Collins S, and Stecher VJ. Sildenafil citrate 100 mg starting dose in men with erectile dysfunction in an international, double-blind, placebo-controlled study: Effect on the sexual experience and reducing feelings of anxiety about the next intercourse attempt. J Sex Med 2009;6:2826,2835. [source]

The Effects Of Tizanidine HCL (Zanaflex®) In Patients With Fibromyalgia

PAIN MEDICINE, Issue 2 2000
Article first published online: 25 DEC 200
David McLain, MD, Brookwood Medical Center, Birmingham, AL This open-label, single-center, dose-finding study of Zanaflex (tizanidine hydrochloride) in 43 patients diagnosed with fibromyalgia showed some effectiveness in reducing pain and other symptoms of this syndrome. Fibromyalgia is a common syndrome characterized by chronic musculoskeletal pain in all 4 quadrants and pain in 18 identified tender points. Effects on fatigue, pain, sleep, and tender points were assessed before and during treatment. Starting doses of 2 mg/day were increased to 4 mg/day after 5 days and increased further as tolerated. Most patients stayed at 4 mg/day or 8 mg/day, and the highest dosage achieved was 12 mg/day. After the initial visit, 6 patients discontinued Zanaflex because of side effects (headaches in 3, hallucinations in 1, hypotension in 1, asthenia in 1), and 11 did not return for a follow-up visit. Results are presented for the remaining 26 patients (25 females; average age 50 years (range, 36,64 years); 25 Caucasian, 1 African-American; 9 on disability or applying for it; all stable on one or more of the following concomitant medications: narcotic analgesics 15%, antidepressants 65%, NSAIDs 46%). On average, at the first follow-up visit (average time 7.8 weeks), patients showed reduction in tender points and improvement on global assessment (GA) scores, Fibromyalgia Impact Questionnaire (FIQ) results, and visual assessment (VAS) scores for fatigue, pain, and sleep. The results for patients still working or retired were better than those for patients on disability or applying for it. Of the 26 patients in this ongoing study, 14 have had second follow-up visits (average time 13.3 weeks). Of these, 2 discontinued the drug at the second follow-up visit. Six of these patients responded especially well to long-term treatment (average age 51 years; range 46,60 years; 5 females; 1 on disability or applying for it) and showed the following averaged results: global assessment improved by 47%, FIQ by 35%, VAS-fatigue by 48%, VAS-pain by 40%, VAS-sleep by 37%, and tender points by 18%. Zanaflex appears to be effective in improving overall functioning, reducing pain and fatigue, improving sleep, and reducing the number of painful tender points in some patients with fibromyalgia, especially in those who are not on disability or applying for it. [source]

Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2004
Peter Paul De Deyn
Abstract Objectives Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings. Methods Patients (n,=,652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5,mg/day). Results Mean age was 76.6±10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items,primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5,mg olanzapine group (,6.2,±,4.9) was significantly greater than with placebo (,5.0,±,6.1, p,=,0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz,2.5 olanzapine group (2.8,±,1.4, p,=,0.030) relative to placebo (3.2,±,1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol. Conclusions While 1.0,mg olanzapine did not show significant differences from placebo, the 2.5,mg dose was a reasonable starting dose. Olanzapine at 7.5,mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2009
G. Derosa MD PhD
Summary Background and objective:, Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods:, We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA1c), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion:, Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion:, Nateglinide improved glycemic control better than glibenclamide in combination with metformin. [source]

Optimizing outcomes with incretin-based therapies: Practical information for nurse practitioners to share with patients

JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2009
BC-ADM, C-RNP, CDE Nurse Practitioner, Evelyne Fleury-Milfort MSN, Instructor in Clinical Medicine
Abstract Purpose: To introduce the role of incretin therapies and suggest strategies for nurse practitioners to implement them in practice. Data sources: PubMed, Medline, summary of product characteristics/package inserts. Conclusions: Incretin-based therapies offer a new alternative to currently available agents. They provide adequate levels of glycemic control and are associated with low incidence of hypoglycemia and weight gain. Dipeptidyl peptidase-4 inhibitors, for example sitagliptin, have a modest effect on A1c levels (,0.7%) as monotherapy; however, they reduce A1c to a greater extent when combined with metformin (,2.0%). Typical starting dose of sitagliptin is 100 mg; dose adjustments are required in subjects with renal complications. Glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, reduce A1c levels (often in excess of 1.5%) and body weight. Exenatide has a starting dose of 5 ,g and is not recommended for patients with hepatic impairment or severe/end-stage renal disease. Liraglutide has been found to benefit from a stepwise dose escalation (i.e., 0.6 mg weekly increments) until a 1.8-mg dose is reached. Unlike exenatide, dose adjustments in patients with renal and hepatic complications are not required. Implications for practice: Incretin-based therapies may help to overcome some of the drawbacks of current therapies used to treat type 2 diabetes. [source]

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003
C Briani
Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26,56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow-up period was 8,6 months (range 2,18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory-motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, "zoster-like" thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow-up and the study of more patients are needed to confirm the results. [source]

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2008
G. LE TRAON
Oral l -thyroxine (l -T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of l -T4 following administration of a solution (Leventa®) was investigated in healthy dogs. l -T4 was absorbed fairly rapidly (tmax 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 ,g l -T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of l -T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with l -T4 oral administration delayed l -T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of l -T4 following administration of a tablet formulation was about 50% of that of the l -T4 solution. The pharmacokinetic properties of liquid l -T4 after oral administration support the use of a dose rate of 20 ,g/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism. [source]

Population pharmacokinetics of pyrazinamide in elephants

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005
M. ZHU
This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20,30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0,24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with Tmax at or before 2 h regardless of the method of drug administration. Cmax at a mean dose of 25.6 (±4.6) mg/kg was 19.6 (±9.5 ,g/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 ± 4.2 mg/kg, Cmax was 25% (4.87 ± 4.89 ,g/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 ± 15.2 mg/kg yielded Cmax of 12.3 ± 6.3 ,g/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher Cmax and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved Cmax values are below the recommended 20,50 ,g/mL range. [source]

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005
J. N. MASLOW
We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form. [source]

Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: The PRACTICE Study

JOURNAL OF VIRAL HEPATITIS, Issue 7 2010
T. Witthoeft
Summary., In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P , 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P , 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P , 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b. [source]

C2 monitoring of cyclosporine in de novo liver transplant recipients: The clinician's perspective

LIVER TRANSPLANTATION, Issue 5 2004
Federico Villamil
Adjusting cyclosporine (CsA) dose based on blood concentration at 2 hours after dose (C2) has been shown in prospective clinical trials to reduce the risk of rejection compared with conventional trough monitoring. In addition, it provides equivalent efficacy to tacrolimus in liver transplant patients, with a favorable safety profile. Target C2 should be defined on an individual basis depending on adjunctive therapy and the level of exposure required. It appears less critical to achieve target C2 in the first few days after liver transplantation than was previously believed. Achieving target C2 exposure in the initial period after transplant requires that changes in the proportion of cyclosporine absorbed from the gut be taken into account to avoid risk of overexposure. In addition, if a starting dose of 10,15 mg/day is used, it is advisable to delay increasing the dose until a trend in C2 level indicates this to be necessary. Immediate dose reduction is required if C2 exceeds target range. In patients with low C2 values, cyclosporine concentration at a later time point should be measured to establish whether the patient is a poor absorber or a delayed absorber of C2, and dose adjustments should be undertaken accordingly. In conclusion, this more flexible approach to C2 monitoring allows the dose of cyclosporine to be individualized effectively for each patient, which results in significant efficacy benefits while minimizing the risk of toxicity. (Liver Transpl 2004;10:577,583.) [source]

Levetiracetam in patients with cortical myoclonus: A clinical and electrophysiological study,

MOVEMENT DISORDERS, Issue 12 2005
Pasquale Striano MD
Abstract Levetiracetam is a new antiepileptic agent that exerts antimyoclonic effects. We conducted an open-label trial to evaluate the effect of levetiracetam in chronic cortical myoclonus of diverse etiologies and to determine whether levetiracetam affects electrophysiological findings. Sixteen patients, aged between 19 and 72 years, with refractory, chronic, cortical myoclonus were recruited. We assessed myoclonus severity with the Unified Myoclonus Rating Scale (UMRS). The electrophysiological study comprised jerk-locked averaging, somatosensory evoked potentials (SEPs), and long loop reflex I. Levetiracetam was administered add-on at a starting dose of 500 mg twice per day up to the target dose of 50 mg/kg/day. Patients were reevaluated clinically and electrophysiologically 2 weeks after the titration phase. Fourteen patients completed the trial. Posttreatment UMRS scores showed an improvement of myoclonus in all cases. Pretreatment, 9 patients had "giant" SEPs. Posttreatment, the amplitude of these SEPs was reduced by more than 50% in 3 of 9 patients, and the mean N20-P25 amplitude was reduced significantly. Pre- and posttreatment SEP amplitude was not related to myoclonus severity or duration. Levetiracetam is a promising and a relatively easy-to-test antimyoclonic agent, which has the potential to improve significantly the patient's disability; however, its long-term efficacy should be verified in larger controlled studies. © 2005 Movement Disorder Society [source]

Efficacy of enteric-coated mycophenolate sodium in patients with active lupus nephritis

NEPHROLOGY, Issue 4 2008
SIU-KA MAK
SUMMARY: Background: The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. Methods: We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. Results: The mean age of the patients was 32.3 ± 11.2 years and the average length of follow up was 25.9 ± 8.9 months. The mean serum creatinine clearance was 93 ± 30.1 mL/min per 1.73 m2 and the mean proteinuria level was 4.5 ± 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 ± 9.7 months with an averaged starting dose of 1350 ± 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 ± 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. Conclusion: Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis. [source]

Intrathecal Ziconotide for Neuropathic Pain: A Review

PAIN PRACTICE, Issue 5 2009
Richard L. Rauck MD
Abstract Neuropathic pain is a considerable burden that affects activities of daily living. The management of neuropathic pain can be challenging because of multiple etiologies and complex manifestations. Ziconotide is a nonopioid intrathecal (IT) analgesic option for patients with neuropathic pain refractory to conventional treatments. The objective of this article is to review the published literature on ziconotide for the treatment of neuropathic pain. Relevant publications were identified through searches of all years of 6 databases, which included PubMed, EMBASE, and CINAHL. Search terms used were ziconotide, SNX-111, MVIIA, Prialt, and neuropathic pain. Publications were included if ziconotide was intrathecally administered (either alone or in combination with other IT agents) to treat neuropathic pain of any etiology and if pain assessment was an outcome measure. Data extracted included study design, IT drug doses, pain outcome measures, and adverse events (AEs). Twenty-eight articles met the inclusion criteria: 5 were preclinical studies and 23 were clinical studies. In the preclinical studies, ziconotide demonstrated antiallodynic effects on neuropathic pain. Data from double-blind, placebo-controlled (DBPC) trials indicated that patients with neuropathic pain reported a mean percent improvement in pain score with ziconotide monotherapy that ranged from 15.7% to 31.6%. A low starting dose and slow titration of ziconotide resulted in an improved safety profile in the aforementioned trials. Common AEs associated with ziconotide include nausea and/or vomiting, dizziness, confusion, urinary retention, and somnolence. Evidence from DBPC trials, open-label studies, case series, and case studies suggests that ziconotide, as either monotherapy or in combination with other IT drugs, is a potential therapeutic option for patients with refractory neuropathic pain. Additional studies are needed to establish the long-term efficacy and safety of ziconotide for neuropathic pain. [source]

Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009
Raman Sood
This clinical trial was conducted to determine the safety and efficacy of bortezomib retreatment in patients with multiple myeloma (MM) who had previously responded to bortezomib. Patients with progressive MM who had previously tolerated bortezomib as a single agent or in combination with other drugs, with a minimum of partial response (PR; ,50% M-protein reduction) for ,4 months, who had not received intervening MM therapy, were retreated with bortezomib (days 1, 4, 8, and 11 of a 21-day cycle) with a starting dose being the dose at which the patient ended the initial treatment. Patients were allowed to receive bortezomib on retreatment in combination with dexamethasone, thalidomide, or doxorubicin. Thirty-two patients received bortezomib retreatment (most with added dexamethasone). The median treatment-free interval (last dose of initial bortezomib treatment to first dose of retreatment) was 9.9 (range 2.5,34.0) months. The median duration of retreatment was 2.8 (<1,7.9) months; median total duration of bortezomib treatment was 6.7 (2.5,19.8) months. Based on the investigators' assessment of best response, the overall response rate (complete plus PR) was 50%. The median time from start of retreatment to progressive disease (PD) was 6.6 (95% confidence interval: 5.1,9.6) months. Thirteen patients (41%) experienced PN; bortezomib-related SAEs were reported in four patients. Retreatment with bortezomib alone or in combination is effective and well tolerated in patients with MM who have responded to their initial bortezomib treatment. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse Attempt

Use of Intradermal Dilutional Testing and Skin Prick Testing: Clinical Relevance and Cost Efficiency

THE LARYNGOSCOPE, Issue 9 2006
Dr. Merritt Seshul MD, FAAOA
Abstract Objectives/Hypothesis: The objective was to determine the agreement of the positive results from a multiple skin prick test (SPT) device with the ability to determine a definable endpoint through intradermal dilutional testing (IDT) to compare semiquantitatively the degree of positivity of SPT results with quantitative results from IDT and to analyze the cost of immunotherapy based on SPT compared with IDT guided by SPT. Study Design: Retrospective review of clinical data (random accrual). Methods: One hundred thirty-four patients underwent allergy screening using a multiple SPT device. Antigens testing positive by skin prick device were tested using IDT on a separate day. Antigens testing negative by SPT were not evaluated by IDT. Regional allergy testing practice patterns were determined, and a cost analysis using Medicare rates was performed Results: There was good agreement between an antigen testing positive by SPT and the determination of a definable endpoint (93.33%, n = 1,334 antigens). The degree of positivity from the SPT correlated poorly with the final endpoint concentration (r = 0.40, P < .0001). Blended testing techniques were similar in cost when compared with several commonly used allergy testing protocols. Conclusions: Antigens which show reactivity to a multiple SPT device usually have a treatable endpoint that is independent of the degree of positivity of the SPT result. IDT is an important step in the determination of the strongest starting dose of immunotherapy that may be safely administered. Initiating immunotherapy in this manner may potentially create significant health care savings by shortening the time required for a patient to reach their individual maximally tolerated dose. The use of a relatively large screening panel is cost effective and does not increase the average number of antigens treated by immunotherapy. Blended allergy testing techniques that include IDT in their protocol are comparable in cost with commonly used allergy testing protocols. [source]

Mycophenolate Blood Level Monitoring: Recent Progress

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
T. Van Gelder
The concentration,effect relationship for mycophenolic acid (MPA), and the high variability in MPA concentrations in patients on standard dose mycophenolate mofetil (MMF) therapy, for some centers has provided enough evidence to implement therapeutic drug monitoring (TDM) for MMF in daily practice. Two randomized trials Adaption de Posologie du MMF en Greffe Renale (APOMYGRE) and fixed-dose versus concentration controlled (FDCC) investigated the added benefit of TDM for MMF in renal transplant recipients. The APOMYGRE study showed a significant reduction in the incidence of acute rejection in concentration-controlled patients, while the FDCC study had a negative outcome, despite a similar study design. Although it was expected that these prospective trials would give the final answer to the question of whether or not TDM for MMF would be of benefit, it seems that the studies have not had much impact on patient management. Several trials have shown the importance of early adequate exposure to MPA in the first week after transplantation. As it will be hard to improve MPA exposure with TDM, this early, ongoing study now investigates the use of an increased starting dose. The increased starting dose will avoid underexposure to MPA in higher proportions of patients shortly after transplantation but may result in more toxicity in patients with MPA exposures exceeding the upper threshold of the therapeutic window. [source]

Recurrent ovarian cancer: Treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experience

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010
Rachel F DEAR
Abstract Aim: To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer. Methods: A retrospective study of 45 patients with recurrent or progressive ovarian cancer was conducted at the Westmead Cancer Care Centre. Patients received PLD at a starting dose of 30,50 mg/m2 every 4 weeks. Results: A total of 43 patients were included for analysis. The starting dose was 40 mg/m2 in 67% of cases, and 21 % had a dose increase. A median of 2 cycles (mean 3, range 1,7) was given. All patients were assessable for response and 77% stopped treatment due to progressive disease. The overall response rate to PLD assessed by CA-125 criteria was 14 percent (six of 43 patients). Five patients (12 percent) were from the potentially platinum-sensitive group and one (2 percent) was from the platinum-resistant group. The overall median progression-free survival was 52 days (2 months), which was greater in the platinum-sensitive than in the platinum-resistant group (4.4 months vs 1.7 months, respectively, P = 0.030). The median overall survival was 296 days (10.6 months) with a trend for this to be longer in the platinum-sensitive than in the platinum-resistant group (13 vs 9 months, P = 0.393). Overall 25 percent of patients had grade 2 or 3 toxicity. Conclusion: The benefit of PLD in platinum-resistant recurrent ovarian cancer is small and the treatment has considerable toxicity. These data support the need to establish whether chemotherapy in this setting has any favorable effect on quality of life. The Australian New Zealand Gynaecological Oncology Group is currently addressing this question in a large prospective study measuring both the subjective and objective benefit (response and survival) of palliative chemotherapy in platinum-resistant or refractory ovarian cancer in Australia. Clinicians are urged to enter their patients in this study to address this important question. [source]

Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008
Jung-Ryul Kim
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers. , The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS , The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach. , The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM. AIMS The aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK). METHODS A population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10,30 mg day,1). RESULTS A one-compartment model with first-order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h,1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/F), reducing the interindividual variability on CL/F from 37.8% CV (coefficient of variation) to 30.5%. The CL/F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20,0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype. CONCLUSIONS This population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated. [source]

Exploring efficacy and tolerability outcomes in patients with difficult-to-treat epilepsy receiving adjunctive topiramate at different titration rates , an exploratory study

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
C. Kurth
Objective,,, To compare rapid vs regular titration of topiramate concerning efficacy and safety. Materials and methods,,, Open-label, prospective, single-center study exploring efficacy and tolerability of two adjunctive dosing regimens of topiramate (TPM) in adult patients with difficult-to-treat epilepsy. Based on investigator judgment, 21 of 50 consecutive patients received a rapid titration (starting dose 50 mg/day, stepwise increase with 50 mg/day after 3 days each until reaching the target dose), while the other 29 patients received titration according to the German prescribing information (starting dose 25 mg/day, stepwise increase with 25,50 mg/day every 7 days). Patients were observed until the target dose was reached and 3 months thereafter. Results,,, Mean final dosages were 136 mg/day (regular titration) and 213 mg/day (rapid titration). Efficacy and tolerability measures did not differ significantly. Forty-six percent of all patients experienced a seizure reduction of ,50%; 14% became seizure free. No serious adverse events occurred. The most common adverse effects were tiredness (20%), memory and language difficulties (18% each), slowness in thinking and speech (10%), psychomotor disturbance (8%) and paresthesia (8%). Conclusions,,, This study suggests that rapid and conventional titration generate similar tolerability, safety and effectiveness in selected patients. [source]

Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance

CANCER, Issue 11 2010
Hagop Kantarjian MD
Abstract BACKGROUND: INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. METHODS: A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. RESULTS: INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and thrombocytopenia. CONCLUSIONS: INNO-406 had anti-CML efficacy in a heavily pretreated study population. On the basis of the classic determinations of both DLT and MTD, the recommended phase 2 dose of oral INNO-406 was 240 mg twice daily. Lower doses of INNO-406 may be equally effective and should be explored. Cancer 2010. © 2010 American Cancer Society. [source]

Thalidomide therapy in adult patients with myelodysplastic syndrome

CANCER, Issue 4 2006
A North Central Cancer Treatment Group phase II trial
Abstract BACKGROUND. Thalidomide has shown promise for the treatment of patients with myelodysplastic syndrome. The current prospective multicenter study examined the efficacy and toxicity of thalidomide in adult patients with myelodysplastic syndrome. METHODS. Using the International Prognostic Scoring System (IPSS), patients were stratified into 2 groups: favorable (IPSS score, 0,1.0) or unfavorable (IPSS score, 1.5,3.5). Seventy-two patients (42 of whom were favorable and 30 of whom were unfavorable) received a starting dose of oral thalidomide of 200 mg daily. The dose was increased by 50 mg per week to a targeted maximum daily dose of 1000 mg. RESULTS. According to the International Working Group response criteria for myelodysplastic syndrome, 1 patient in the unfavorable group achieved a partial remission with a complete cytogenetic response. Overall, 2 patients (5%) in the favorable group and 4 patients (14%) in the unfavorable group experienced either a hematologic improvement or a partial response. The most frequent Grade 3 or 4 (grading was based on the National Cancer Institute's Common Toxicity Criteria [version 2.0]) nonhematologic adverse events were fatigue (24%), infection (19%), neuropathy (13%), dyspnea (8%), and constipation (7%). CONCLUSIONS. Thalidomide alone, at the schedule and dose levels used in the current study, is not a safe and viable therapeutic option for patients with myelodysplastic syndrome. Limited efficacy and increased toxicity were observed in the current Phase II trial. Cancer 2006. © 2006 American Cancer Society. [source]

Clinical and Experimental Aspects of Olmesartan Medoxomil, a New Angiotensin II Receptor Antagonist

CARDIOVASCULAR THERAPEUTICS, Issue 4 2004
Kazunori Yoshida
ABSTRACT Olmesartan medoxomil is a new orally active angiotensin II (Ang II) type 1 receptor antagonist. It is a prodrug and is rapidly de-esterified during absorption to form olmesartan, the active metabolite. Olmesartan is a potent, competitive and selective Ang II type 1 receptor antagonist. Olmesartan is not metabolized by the cytochrome P-450 and has a dual route of elimination, by kidneys and liver. In patients with essential hypertension olmesartan medoxomil administered once daily at doses of 10,80 mg dose-dependently reduced diastolic blood pressure (DBP). Troughto-peak ratios for both DBP and systolic blood pressure (SBP) were above 50%. At the recommended once-daily starting doses, olmesartan medoxomil (20 mg) was more effective than losartan (50 mg), valsartan (80 mg) or irbesartan (150 mg) in reducing cuff DBP in patients with essential hypertension. The results of cuff SBP and mean 24-h DBP and SBP were similar to those of cuff DBP measurement. In mild-to-moderate hypertensive patients the recommended starting dose of olmesartan medoxomil was as effective as that of amlodipine besylate (5 mg/day) in reducing both cuff and 24-h blood pressure. In lowering DBP olmesartan medoxomil, at 10,20 mg/day, was as effective as atenolol at 50,100 mg/day. In mild-to-moderate hypertensive patients, olmesartan medoxomil, at 5,20 mg once daily, was more effective than captopril at 12.5,50 mg twice daily. At 20,40 mg once daily olmesartan medoxomil was as effective as felodipine, at 5,10 mg once daily. Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models. Future investigation should reveal whether these beneficial effects of olmesartan medoxomil are applicable to human diseases. [source]

Use of inhaled nitric oxide in the new born period: results from the European inhaled nitric oxide registry

ACTA PAEDIATRICA, Issue 6 2010
Chris Dewhurst
Abstract Aims:, The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Methods:, Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). Results:, A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Conclusion:, Collating and reporting data about iNO therapy in neonates across a number of European centres using a web-based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO. [source]

Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation

CLINICAL TRANSPLANTATION, Issue 4 2007
Andrew A. House
Abstract:, Bioavailability and exposure of cyclosporine microemulsion and tacrolimus in renal transplantation are governed by many complex factors. Failure to achieve therapeutic two-h post-dose (C2) levels despite adequate doses of cyclosporine ("low absorbers") may merit conversion to tacrolimus. We compared tacrolimus dose requirements in "low absorbers" (n = 15) with a random control group of de novo tacrolimus patients (n = 14). Low absorbers failed to reach target C2 despite increasing dose from 10.1 to 16.2 mg/kg/d. At conversion the mean C2 was 969 ng/mL (95% CI: 684,1255; target 1700 ng/mL). Low absorbers tended to be younger, heavier, and diabetic. Despite a similar initial tacrolimus dose (0.17,0.18 mg/kg/d), low absorbers required a much higher daily dose to achieve target; 0.25 vs. 0.16 mg/kg/d (p = 0.016). Furthermore, daily maintenance tacrolimus remained much higher in low absorbers at three wk (0.22 vs. 0.13 mg/kg/d, p = 0.012). Although not statistically significant, this group experienced an acute rejection rate of 33%, compared with 21% in the control group. Patients treated with cyclosporine as initial immunosuppression who fail to reach target C2 levels in a timely fashion are at risk for impaired bioavailability of tacrolimus. Based on our data, a starting dose of 0.25 mg/kg/d in divided doses may be warranted for low absorbers converting to tacrolimus; however, we encourage larger studies with formal pharmacokinetic analysis in this population. [source]

Obesity, hyperlipidemia, and metabolic syndrome

LIVER TRANSPLANTATION, Issue S2 2009
Michael Charlton
Key Points 1. Obesity is increasingly common among liver transplantation (LT) recipients and donors. Outcomes following LT for selected patients with class I-III obesity are similar to those for nonobese recipients. In patients who are otherwise satisfactory candidates for LT, a high body mass index, as long as it does not present a technical barrier, should not be considered to be an absolute contraindication to LT. 2. The most common causes of death beyond the first year of LT are, in descending order of frequency, graft failure (especially secondary to hepatitis C virus recurrence), malignancy, cardiovascular disease, infections, and renal failure. Metabolic syndrome is an important risk factor for each of these etiologies of posttransplant death. Posttransplant diabetes, posttransplant hypertension, and an original diagnosis of cryptogenic cirrhosis, which is commonly associated with metabolic syndrome, are all associated with an increased risk of post-LT mortality. Features of metabolic syndrome should be screened for and treated in LT recipients. 3. Because of the physiological mechanism of post-LT hypertension, which includes renal arteriolar constriction secondary to calcineurin inhibition, calcium channel blocking agents are a good pharmacological treatment modality and have been shown to be effective in renal protection in randomized controlled trials of posttransplant hypertension. 4. It is rare for dietary changes and weight reduction to result in normalization of the lipid profile. Statins should thus be initiated early in the course of management of post-LT dyslipidemia. Forty milligrams of simvastatin per day, 40 mg of atorvastatin per day, and 20 mg of pravastatin per day are reasonable starting doses for post-LT hypercholesterolemia. It is important to remember that the effects of statin therapy are additive to those of a controlled diet (eg, a Mediterranean diet rich in omega-3 fatty acids, fruits, vegetables, and dietary fiber). 5. Nonalcoholic steatohepatitis, an increasingly common etiology of cirrhosis and liver failure, recurs commonly after LT and may also arise de novo. Treatment should be directed at managing obesity and complications of metabolic syndrome. Optimal immunosuppression in patients with nonalcoholic steatohepatitis is still evolving but should include steroid minimization. Liver Transpl 15:S83,S89, 2009. © 2009 AASLD. [source]

Insulin initiation among adults and children with diabetes in the United Kingdom

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 4 2006
NDNCert, PGCE Head of Department (Integrated Health, RE Davis MPhil, Social Care)
Abstract There is no doubt that insulin therapy is effective in the management of people with diabetes. Indications for the use of insulin are agreed, but wide variations exist in the practice of starting people with diabetes on insulin. Current health care practices in the United Kingdom are increasingly being based on scientific evidence. This literature review concentrates on current insulin initiation practice, examining the evidence base for the insulin regimens used, the process for determining starting doses and the decision making process involved. It concludes that there are wide variations in practice among the multidisciplinary team and that there is little published regarding the commencement of people with type 2 diabetes on insulin. It is likely that custom and habit still play a large role in current practice. Copyright © 2006 John Wiley & Sons, Ltd. [source]