Pharmacokinetics of single-dose rosiglitazone in chronic ambulatory peritoneal dialysis patients.

BACKGROUND: End-stage renal disease (ESRD) is associated with marked alterations in the pharmacokinetics of many drugs, not only from reduction in renal clearance but also from changes in metabolic activity, bioavailability, volume of distribution and plasma protein binding. OBJECTIVE: To study the pharmacokinetics of a single 8-mg oral dose of rosiglitazone in patients with ESRD and requiring long-term chronic ambulatory peritoneal dialysis (CAPD). METHOD: The medication was administered just before the first exchange of peritoneal dialysis fluid on the day that blood and peritoneal dialysate collection was performed. RESULTS: In our CAPD patients the mean (+/-SD) T(max) and T(1/2) of rosiglitazone were 1.20 +/- 0.26 and 21.38 +/- 21.96 h respectively. These values were different to those reported for healthy volunteers reported in previous studies. The mean area under the concentration-time curve (AUC((0-infinity))) and an average maximum observed plasma concentration (C(max)) of rosiglitazone in our CAPD patients were 4203.56 +/- 2916.97 ng h/mL and 409.67 +/- 148.89 ng/mL respectively. These appear no different from those reported in healthy volunteers . CONCLUSION: The apparently significant difference in T(1/2) of rosiglitazone in CAPD patients compared with healthy volunteers suggest that dose adjustment may be necessary in order to avoid toxicity.

Bioequivalence study of clindamycin phosphate injection (Clinott-P) in Thai healthy volunteers.

BACKGROUND AND OBJECTIVE: Generic clindamycin given intramuscularly, should have identical active ingredient(s), strength, and demonstrable bioequivalence to those of original product. The aim of this investigation was to compare the bioavailability of a single, intramuscular injection, of 2 ml. of 300 mg. of a generic clindamycin (Clinott-P) and the original preparation (Dalacin C). MATERIAL AND METHOD: A randomized, double-blinded, crossover study was conducted. Twenty-four healthy males were recruited at Siriraj Hospital and randomized to receive a single intramuscular injection of either Clinott-P or Dalacin C. Treatment was followed by a two-week washout period. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours after the injection. Plasma samples were analysed for clindamycin by a validated HPLC method at the Faculty of Pharmaceutical Sciences, Chulalongkorn University. RESULTS: Twenty-four volunteers enrolled in and completed the study. They exhibited an average height of 167.92 cm (SD = 5.82), weight of 60.10 kg (SD = 7.36), body mass index of 21.27 (SD = 1.73) and normal blood chemistries. The Cmax of Clinott-P was 3.94225 microg/ml at Tmax 1.75 hours and of Dalacin C, 3.6847 microg/ ml at Tmax 2.09 hours. The AUC0-24 of Clinott-P was 16.32 +/- 6.13 micro.hr/ml and Dalacin C was 17.24 +/- 7.46 microg.hr/ml. Ninety percent confidence intervals of the mean ratios (test/reference) of log transformed of Cmax (93.07-123.43%), AUC(0-24) (82.58-112.31%) and AUC(0-inf), (81.54-110.06%) were all within the standard range (80-125 %) for bioequivalence study. Tenderness after injection around the deltoid area was assessed blindly and was found to be slight (visual basic score < 5) and presented for one or two days after the injection. CONCLUSION: The two brands of clindamycin exhibit comparable pharmacokinetic parameters and volunteers exhibited slight and tolerable tenderness at the injection site.