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Increased Dose (increased + dose)
Selected AbstractsElderly patient presenting with severe thyrotoxic hypercalcemiaGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2006Reiko Kikuchi An 81-year-old woman with Graves' disease and osteoporosis was referred to the hospital because of anorexia over one month and impaired consciousness. She also presented with low-grade fever and emaciation. Laboratory tests revealed marked hypercalcemia (corrected serum calcium level of 12.4 mg/dL), which was initially suspected to result from vitamin D toxicity, because she had been taking vitamin D3 (alphacalcidol of 0.5 µg/day) for the treatment of osteoporosis. However, discontinuation of vitamin D3 and fluid infusion did not ameliorate hypercalcemia one week later. After excluding hyperparathyroidism and malignancy-related hypercalcemia, hypercalcemia was considered to be attributable to the exacerbation of hyperthyroidism (free T4 of 6.69 ng/dL, free T3 of 13.27 pg/mL and thyroid stimulating hormone (TSH) <0.015 µIU/mL) with increased bone resorption. Finally, the increased dose of thiamazole (30 mg/day) normalized serum calcium level and thyroid function three months later. Laboratory tests suggested that normal bone formation in spite of increased bone resorption contributed to hypercalcemia in hyperthyroid state. [source] Lopinavir protein binding in HIV-1-infected pregnant womenHIV MEDICINE, Issue 4 2010FT Aweeka Background Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and ,-1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to ,1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously. Methods P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP. Results AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96±0.16% AP vs. 0.82±0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG. Conclusions LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy. [source] Cholinesterase inhibitors in advanced Dementia with Lewy bodies: increase or stop?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2006Sanjeet Pakrasi Abstract Introduction There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. Method We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15,mg) to resolve re-emergent neuropsychiatric symptoms. Results The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. Conclusion Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hepatitis C: Retreatment and treatment of patients with renal failureJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Wan-Cheng Chow This paper addresses two difficult issues in the treatment of hepatitis C: patients who fail to achieve a sustained response after the first course of treatment, and those who simultaneously suffer from chronic renal failure. With the recent improvements in firstline treatment, retreatment is mainly applicable to those who have previously received 6-month of interferon monotherapy at 3 MU thrice weekly. For those who had an end-of-treatment response but relapsed, there is a choice between interferon monotherapy at increased dose and/or duration of treatment, or a 6-month course of combination therapy. Retreatment of non-responders is generally unsuccessful, but some patients may respond to interferon-alpha 3 MU and ribavirin 1.0,1.2 g/day. For patients with chronic renal failure and hepatitis C, combination treatment is not possible because ribavirin is contraindicated. Interferon given at a dose of 1.5 MU thrice weekly was reported to be fairly well tolerated by patients who were on dialysis and resulted in end-of-treatment and sustained biochemical and virological response in some cases. Interferon given in the usual doses may be associated with severe adverse effects in patients with renal failure, and can precipitate allograft rejection in patients who have undergone renal transplantation. [source] An investigation of dose titration with darifenacin, an M3 -selective receptor antagonistBJU INTERNATIONAL, Issue 4 2005William Steers OBJECTIVES To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M3 -selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS In this multicentre double-blind 12-week study, 395 patients (aged 22,89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at ,,8.2 (,62.9%) and ,,6.0 (,48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P=,0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for ,sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in <,3.0% of darifenacin-treated patients and <1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs. [source] Evaluation of vitreous levels of gatifloxacin after systemic administration in inflamed and non-inflamed eyesACTA OPHTHALMOLOGICA, Issue 6 2009Rajpal Abstract. Purpose:, This study aimed to evaluate the human vitreous penetration of gatifloxacin in inflamed and non-inflamed eyes after oral administration. Methods:, Vitreous penetration of single-dose (400 mg) oral gatifloxacin was evaluated in patients (n = 33) undergoing vitreous tap during the standard procedure for intravitreal antibiotic injection for acute postoperative endophthalmitis at various time-points. Vitreous penetration of 400 mg oral gatifloxacin was evaluated in the non-inflamed eyes of patients (n = 33) undergoing pars plana vitrectomy at similar time-points. The study was extended to evaluate the vitreous penetration of single-dose oral (800 mg) gatifloxacin at a single time-point in inflamed (n = 10) and non-inflamed (n = 11) eyes. Results:, After 400 mg oral gatifloxacin, inflamed eyes showed mean vitreous concentrations of 0.58±0.19,g/ml, 1.33±0.33 ,g/ml and 1.30 ± 0.23 ,g/ml at 2, 4 and 6 hours, respectively. The levels reached at 2 and 4 hours were found to be significantly increased compared with those in non-inflamed eyes. At the 800-mg dose, 4-hour vitreous levels in inflamed and non-inflamed eyes were 1.57 ± 0.3 ,g/ml and 1.42 ± 0.24 ,g/ml, respectively. Although the increased dose of gatifloxacin elevated plasma concentration, it failed to raise vitreous levels significantly higher than the 400-mg dose at the 4-hour time-point. Conclusions:, Orally administered gatifloxacin achieves therapeutic levels in both inflamed and non-inflamed human eyes with a spectrum covering the bacterial species most frequently involved in the various causes of endophthalmitis. However, the levels achieved were below the MIC90 for Pseudomonas aureginosa and Enterococcus. [source] | ||||||||||