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Daily Dosing (daily + dosing)
Selected AbstractsIbandronate: A Comparison of Oral Daily Dosing Versus Intermittent Dosing in Postmenopausal OsteoporosisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001B. J. Riis Abstract The objective of this study was to compare efficacy and safety of continuous versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55,75 years with postmenopausal osteoporosis were randomized to active treatment or placebo. Similar total doses of ibandronate were provided by treatment regimens with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg of ibandronate every other day for the first 24 days, followed by 9 weeks without active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12 months to receive either continuous (n = 37) or intermittent ibandronate (n = 35). By 24 months, bone mineral density (BMD) had increased significantly relative to baseline in both active treatment groups. The continuous and intermittent groups showed statistically equivalent increases in lumbar spine BMD of +5.64% (±0.53) and +5.54% (±0.53) and in total hip of +3.35% (±0.40) and +3.41% (±0.40), respectively (per protocol population). Biochemical markers of bone turnover decreased significantly in both treatment groups. The level of marker suppression was similar, although the intermittent group displayed, as expected, more fluctuation over the treatment period. The frequency of adverse events was similar in the treatment groups. In conclusion, the intermittent and continuous regimens showed equivalent changes in BMD and bone turnover. These results confirm previous preclinical findings indicating that the efficacy of ibandronate depends on the total oral dose given rather than on the dosing schedule. This supports development of new flexible dosing regimens targeted to minimize the frequency of dosing, which are expected to improve convenience and lead to enhanced long-term patient compliance. [source] A review of basal insulinsDIABETIC MEDICINE, Issue 11 2003Anthony H. Barnett Abstract Tight glycaemic control (ideally, HbA1c < 7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes. [source] Clinical issues in using buprenorphine in the treatment of opiate dependenceDRUG AND ALCOHOL REVIEW, Issue 3 2000Dr A. Chadderton MB Abstract This paper looks at the current role of buprenorphine in the treatment of opiate dependence. It suggests that buprenorphine is a useful alternative to methadone and that in at least some cases it may be the preferred option. Buprenorphineis a partial agonist and a partial antagonist with a ceiling of opiate activity probably approximately equal to 30mg methadone. It achieves this at a dose of 10-12mg, although there is considerable individual variation. Because of its ceiling effect it has a good safety profile compared to full agonists such as methadone although some overdose deaths, particularly in conjunction with benzodiazepine abuse, have been reported in France. Induction of buprenorphine may take slightly longer than for methadone and there is a higher dropout rate compared to methadone in the first 2 weeks. This is probably due to the antagonist action of buprenorphine causing more withdrawal symptoms in comparison to methadone. Also, the ceiling effect for buprenorphine means that some clients do not experience sufficient opiate activity to satisfy them. Buprenorphine has a long half-life and dissociates slowly from opiate receptors. Most clients can be dosed second-daily but some find this unacceptable due to mood swings and/or withdrawal symptomson the second day. For these clients daily dosing is required. Transferring from buprenorphine to methadone is straightforward and well tolerated by clients. Transferring from methadone to buprenorphine, however, is more difficult because of the partial antagonist action of buprenorphine. Clients experience withdrawal symptoms that can take up to 2 weeks to settle. Most clients find these symptoms unacceptable when transferring from doses of over 30mg of methadone. The optimum method for transferring from methadone to buprenorphine is still to be determined. Withdrawal from buprenorphine appears to be relatively easier than from methadone. This is presumably due to buprenorphine's partial agonist effect at mureceptors. It is expected that during 2000 buprenorphine will be approved for use in Australia for the treatment of opiate dependence. It may well becomea first-line choice for opiate replacement in heroin dependence. It is also likely to be useful in assisting detoxification fromboth methadone and heroin. [source] Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2001Dr. Per G. Farup Abstract Background High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. Methods Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index; UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than ,1 UC-DAI score unit. Results Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. Conclusion Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing. [source] PDE5 inhibitors in diabetic peripheral neuropathyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2006G. HACKETT Summary Peripheral neuropathy is the most common complication of diabetes. This paper reviews the case histories of five patients with diabetic peripheral neuropathy or severe peripheral vascular disease who reported improvement in their symptoms when treated with regular or daily dosing with phosphodiesterase type 5 inhibitors (PDE5Is). These patients had been previously treated with PDE5Is for erectile dysfunction (ED) and not responded to on-demand therapy with a PDE5I at maximal recommended dose. This improvement is likely to be due to the known benefit of these drugs on endothelial dysfunction via an improvement of blood supply to the vasa nervorum. These cases suggest that further research is indicated to evaluate the potential use of PDE5Is in the treatment and prevention of diabetic peripheral neuropathy, particularly as these drugs are already licensed to treat ED, which occurs in around 50% of male diabetics. [source] Two-Year Results of Once-Weekly Administration of Alendronate 70 mg for the Treatment of Postmenopausal OsteoporosisJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002R Rizzoli Abstract The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42,95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6, 7.5), and 7.4% (6.9, 7.8) at the lumbar spine and 4.1% (3.8, 4.5), 4.3% (3.9, 4.7), and 4.3% (3.9, 4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy. [source] Aminoglycoside dosing in diabetesJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2000Axworthy Studies have evaluated the comparative efficacy, toxicity and costs associated with extended-interval vs. standard multiple daily dosing of aminoglycosides. In this case, an elderly man with diabetes and good renal function at baseline was switched from standard to extended-interval dosing. During the course of therapy there was evidence of decreased renal function. Pertinent literature was searched for, uncovered and critically evaluated to determine if and what evidence supports using extended dosing of aminoglycosides in this population. No data were found specifically evaluating the different dosing strategies in diabetic patients. However, there were many trials and several meta-analysis located that compared the two dosing strategies, most suggesting at least a cost advantage and possibly less toxicity with extended-interval dosing. Further information is needed to determine whether there is a differential risk for toxicity between these dosing regimens in patient with diabetes. [source] A dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol)ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009M. P. THORPE Summary Backround, 5-ASA in a pH sensitive tablet (Asacol) is administered as three doses/day to treat ulcerative colitis. Once daily dosing may improve patient adherence. Simulation of colonic levels of 5-ASA can be used to compare dosing regimens. Aim, To create a dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol). Methods, Using published data, we created a computer model with STELLA software to simulate amounts of colonic 5-ASA in the total colon, right, transverse, descending and sigmoid/rectum after daily and three time/day Asacol. Results, The model predicted similar total and regional amounts of 5-ASA with both regimens. Distribution of 5-ASA was 38% in the right colon, 33% in the transverse colon and 14% each in the descending and sigmoid/rectal colon. Simulated increases in colonic motility and defecation rate exaggerated this 5-ASA distribution, resulting in negligible amounts of 5-ASA in the sigmoid/rectal region. Conclusions, This computer model suggests that Asacol can be administered as a single daily dose. The model supports experimental and clinical observations that alternate dose or route of administration may be necessary to achieve adequate 5-ASA amounts in the distal colon during acute exacerbations of ulcerative colitis. This simulation cannot account for all sources of variability in the clinical setting, but provides a rationale for further investigation. [source] Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2005D. Castell Summary Background :,Many patients treated with a proton-pump inhibitor for gastro-oesophageal reflux disease or erosive oesophagitis still have substantial night-time gastric acidity. A previous trial of a new immediate-release omeprazole oral suspension suggested that nocturnal gastric acidity could be more effectively controlled with a bedtime dose of immediate-release omeprazole than with a delayed-release proton-pump inhibitor administered before dinner or at bedtime. Aim :,To compare the ability of immediate-release omeprazole with pantoprazole to control nocturnal gastric acidity, when they were dosed once daily and twice daily. Methods :,Thirty-six patients with nocturnal gastro-oesophageal reflux disease symptoms received immediate-release omeprazole and pantoprazole in this open-label, randomized-crossover trial. Median gastric pH, the percentage of time with gastric pH > 4 and the percentage of patients with nocturnal acid breakthrough, were evaluated with 24-h pH monitoring. Results :,Repeated once daily (bedtime) dosing with immediate-release omeprazole suspension produced significantly better nocturnal gastric acid control than repeated once daily (predinner) or twice daily (prebreakfast and bedtime) dosing with pantoprazole delayed-release tablets (median pH: 4.7 vs. 2.0 and 1.7; percentage of time pH > 4: 55 vs. 27 and 34; nocturnal acid breakthrough: 53 vs. 78 and 75). Twice daily dosing (prebreakfast and bedtime) with immediate-release omeprazole 20 and 40 mg achieved the best night-time control of gastric acidity. Repeated once daily bedtime dosing with immediate-release omeprazole 40 mg and twice daily dosing with pantoprazole 40 mg gave similar 24-h pH control. No safety issues were associated with either drug in this trial. Conclusions :,Dosed once daily at bedtime, immediate-release omeprazole reduced nocturnal gastric acidity to a degree not observed with once daily dosing of delayed-release proton-pump inhibitors. [source] Cyclosporine exposure and calcineurin phosphatase activity in living-donor liver transplant patients: Twice daily vs. once daily dosingLIVER TRANSPLANTATION, Issue 2 2006Masahide Fukudo We have compared the pharmacokinetics and pharmacodynamics of cyclosporine between once- and twice-daily dosing regimens in de novo patients of living-donor liver transplantation (LDLT). A total of 14 patients were enrolled in this study, who had received cyclosporine microemulsion (Neoral) twice a day (BID, n = 5) or once daily in the morning (QD, n = 9) after transplantation. On postoperative day (POD) 6, the QD regimen significantly increased cyclosporine exposure; the blood concentration at 2 hours postdose (C2) and area under the concentration-time curve (AUC) for 4 hours (AUC0,4), compared with the BID regimen. Moreover, the area under the calcineurin (CaN) activity in peripheral blood mononuclear cells time-curve (AUA) for 12 hours (AUA0,12) and 24 hours (AUA0,24) were decreased by approximately 42 and 25% with the QD regimen relative to the BID regimen, respectively. The C2 level was significantly correlated with the AUC0,4 (r2 = 0.95), which was negatively related to the AUA0,12 with a large interindividual variability (r2 = 0.59). However, a significant correlation was found between the AUA0,12 or AUA0,24 and CaN activity at trough time points. According to a maximum inhibitory effect attributable to the drug (Emax) model, the mean estimates of Emax and the Cb value that gives a half-maximal effect (EC50) for CaN inhibition were not significantly different between the 2 groups, respectively. These findings suggest that a once daily morning administration of cyclosporine may improve oral absorption and help to provide an effective CaN inhibition early after LDLT. Furthermore, CaN activity at trough time points would be a single surrogate predictor for the overall CaN activity throughout dosing intervals following cyclosporine administration. Liver Transpl 12:292,300, 2006. © 2006 AASLD. [source] Urologist Practice Patterns in the Management of Premature Ejaculation: A Nationwide SurveyTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2008Alan Shindel MD ABSTRACT Introduction., Contemporary U.S. urologist's "real world" practice patterns in treating premature ejaculation (PE) are unknown. Aim., To ascertain contemporary urologist practice patterns in the management of PE. Method., A randomly generated mailing list of 1,009 practicing urologists was generated from the American Urologic Association (AUA) member directory. A custom-designed survey was mailed to these urologists with a cover letter and a return-address envelope. Responses were compared with the AUA 2004 guidelines for the treatment of PE. Main Outcome Measures., The survey assessed several practice-related factors and asked questions of how the subject would handle various presentations of PE in their practice. Results., Responses from practicing urologists totaled 207 (21%). Eighty-four percent of the respondents were in private practice and 11% were in academics. Most urologists (73%) saw less than one PE patient per week. On-demand selective serotonin reuptake inhibitor (SSRI) therapy was the most commonly selected first line treatment (26%), with daily dosing a close second (22%). Combination SSRI therapy, the "stop/start" technique, the "squeeze" technique, and topical anesthetics were favored by 13, 18, 18, and 11% of the respondents, respectively. If primary treatment failed, changing dosing of SSRIs, topical anesthetics, and referral to psychiatry were increasingly popular options. Ten percent of urologists would treat PE before erectile dysfunction (ED) in a patient with both conditions, with the remainder of the respondents treating ED first, typically with a phosphodiesterase type 5 inhibitor (78% of total). Fifty-one percent of urologists report that they would inquire about the sexual partner, but only 8, 7, and 4% would evaluate, refer, or treat the partner, respectively. Conclusions., The majority of our respondents diagnose PE by patient complaint, and treat ED before PE, as per the 2004 PE guidelines. Very few urologists offer referral or treatment to sexual partners of men suffering from PE. Additional randomized studies in the treatment of PE are needed. Shindel A, Nelson C, and Brandes S. Urologist practice patterns in the management of premature ejaculation: A nationwide survey. J Sex Med 2008;5:199,205. [source] A pilot dose-escalation study of the effects of nordihydroguareacetic acid on hormone and prostate specific antigen levels in patients with relapsed prostate cancerBJU INTERNATIONAL, Issue 4 2008Charles J. Ryan OBJECTIVE To assess the tolerability of the effects of nordihydroguareacetic acid (NDGA) and its effect on prostate-specific antigen (PSA) kinetics in patients with relapsed prostate cancer, as among the many biological effects of NDGA is the inhibition of the insulin-like growth factor 1 receptor (IGF-1R) tyrosine kinase. PATIENTS AND METHODS Eligible patients were those with an increasing PSA level after definitive local therapy, in either the non-castrate (androgen-dependent prostate cancer, ADPC) or the castrate state (castration-resistant prostate cancer, CRPC) with no evidence of metastatic disease by bone scan or computed tomography of the abdomen or pelvis. Treatment consisted of continuous oral daily dosing according to a planned dose escalation of 750, 1250, 1750, 2250 and 2500 mg of NDGA. PSA levels were measured every 28 days. Serial levels of testosterone, dihydrotestosterone, oestradiol and sex hormone-binding globulin were measured at baseline and monthly while on study therapy. RESULTS Fifteen patients were enrolled, including 11 with ADPC and four with CRPC. There were asymptomatic increases in transaminase in six patients, two of which were grade 3, all occurring at ,3 months. The increases in transaminase resolved after stopping NDGA but recurred with repeated dosing. Doses of NDGA up to 2500 mg/day caused no other toxicities. A median (range) of 5.5 (1,13) cycles were delivered. Of the 11 patients with ADPC, one had a decline in PSA level of >50% of the baseline value and one a decline of <50%. Three patients with ADPC had a greater than three-fold increase in PSA doubling time while on therapy, one from 11 to 46 months (750 mg), one from 9.5 to 49.5 months (1750 mg), and one from 5.9 to 46.2 months (2500 mg). There were no reductions in PSA level in patients with CRPC. There were no significant effects on levels of testosterone, dihydrotestosterone, oestradiol or sex hormone-binding globulin. CONCLUSIONS Continuous daily dosing with NDGA is reasonably well tolerated but is associated with transaminitis in some patients, that occurs after several months on therapy. There were apparent effects on the rate of increase in PSA. Further study is required to determine the optimum pharmacokinetics and antitumour effects of this therapy. [source] Hormonal and metabolic effects of morning or evening dosing of the dipeptidyl peptidase IV inhibitor vildagliptin in patients with type 2 diabetesBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Yan-Ling He WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Vildagliptin is an orally active, potent inhibitor of dipeptidyl peptidase IV and was developed for the treatment of type 2 diabetes. , In clinical trials, once or twice daily dosing with vildagliptin (up to 100 mg day,1) has been shown to reduce endogenous glucose production and fasting plasma glucose in patients with type 2 diabetes. , The comparative efficacy of vildagliptin under a morning vs. evening dosing regimen has not previously been determined. WHAT THIS STUDY ADDS , Once daily dosing with vildagliptin 100 mg for 28 days improved glycaemic control in patients with type 2 diabetes independent of whether vildagliptin was administered in the morning or evening. , Morning or evening dosing with vildagliptin had similar effects on 24 h glycaemic control and plasma concentrations of the hormones insulin, glucagon and glucagon-like peptide 1. AIM This randomized, double-blind, crossover study compared post-prandial hormonal and metabolic effects of vildagliptin, (an oral, potent, selective inhibitor of dipeptidyl peptidase IV [DPP-4]) administered morning or evening in patients with type 2 diabetes. METHODS Forty-eight patients were randomized to once daily vildagliptin 100 mg administered before breakfast or before dinner for 28 days then crossed over to the other dosing regimen. Blood was sampled frequently after each dose at baseline (day ,1) and on days 28 and 56 to assess pharmacodynamic parameters. RESULTS Vildagliptin inhibited DPP-4 activity (>80% for 15.5 h post-dose), and increased active glucagon-like peptide-1 compared with placebo. Both regimens reduced total glucose exposure compared with placebo (area under the 0,24 h effect,time curve [AUE(0,24 h)]: morning ,467 mg dl,1 h, P= 0.014; evening ,574 mg dl,1 h, P= 0.003) with no difference between regimens (P= 0.430). Reductions in daytime glucose exposure (AUE(0,10.5 h)) were similar between regimens. Reduction in night-time exposure (AUE(10.5,24 h) was greater with evening than morning dosing (,336 vs.,218 mg dl,1 h, P= 0.192). Only evening dosing significantly reduced fasting plasma glucose (,13 mg dl,1, P= 0.032) compared with placebo. Insulin exposure was greater with evening dosing (evening 407 µU ml,1 h; morning 354 µU ml,1 h, P= 0.050). CONCLUSIONS Both morning and evening dosing of once daily vildagliptin 100 mg significantly reduced post-prandial glucose in patients with type 2 diabetes; only evening dosing significantly decreased fasting plasma glucose. Although evening dosing with vildagliptin 100 mg tended to decrease night-time glucose exposure more than morning dosing, both regimens were equally effective in reducing 24 h mean glucose exposure (AUE(0,24 h)) in patients with type 2 diabetes. [source] | ||||||||||