Bioequivalence study of generic gliclazide and Diamicron formulations in healthy Thai male volunteers.

UNLABELLED: The objective of this study was to compare the bioequivalence of 80 mg gliclazide in healthy Thai males. A single dose of each preparation was administered after an overnight fast in a 2-period crossover design with a 2-week washout period. Serial blood samples were collected over a period of 60 hours. Plasma gliclazide concentrations were determined using HPLC and the pharmacokinetic parameters were analyzed by non-compartmental analysis. RESULTS: The median time to reach the maximal concentration (Tmax) for the test formulation was identical to that of the reference Diamicron (11.5 h). Similarly, the mean elimination half-lives (t1/2) for the test (20.4 +/- 7.8 h) and Diamicron (21.5 +/- 9.4 h) were comparable. Analysis of variance was carried out using logarithmic transformations of AUC(0-infinity) and Cmax as well as non-transformed Tmax. The mean (90% CI) of the difference in Tmax (h) was 0.08 ((-1.44)-1.61). The mean (90% CI) of the AUC(0-infinity) and Cmax ratios for (test/reference) were 1.08 (0.98-1.18) and 1.09 (0.89-1.34), respectively. Since these values fall within the bioequivalence criteria, our study demonstrates bioequivalence of the 2 products.

Protective effects of fosfomycin on cisplatin-induced nephrotoxicity in patients with lung cancer.

SUBJECTS, MATERIAL AND METHODS: Protective effects of fosfomycin on cisplatin-induced nephrotoxicity have been previously reported, however, the proper time, duration and dosage of its administration were uncertain. Therefore, we investigated the protective effect of concurrent administration of twice-daily doses of 2 g fosfomycin for 5 days in 13 cisplatin-naïve lung cancer patients who were due to receive a single dose per cycle of 100 mg/m2 cisplatin. On each chemotherapeutic cycle, patients were randomly given cisplatin alone or cisplatin plus fosfomycin every 4 weeks for a maximum of 4 consecutive cycles. Indicators of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, serum creatinine (Scr) and creatinine clearance (Clcr) were determined the day before and at day 3 and day 6 after cisplatin administration. Results were compared and statistically analyzed by the non-parametric Mann-Whitney's test. We found that the NAG activities obtained on day 0, day 3 and day 6 of the fosfomycin cycles were comparable to values obtained during the control cycles (p > 0.05). Moreover, the NAG activities on day 3 of both treatment cycles were significantly elevated from baseline (p < 0.01) and had normalized on day 6. There were no significant changes in serum creatinine and creatinine clearance. CONCLUSION: High-dose cisplatin induced reversible elevation of urinary NAG and concurrent administration of low-dose fosfomycin for 5 days had no effect on the enzymuria. In the prevention of cisplatin nephrotoxicity, a further study using dose escalation (8 to 12 g/d) of fosfomycin administered 2 to 3 days prior to cisplatin are required to demonstrate its nephroprotective effects.

Pharmacokinetics and bioequivalence testing of generic fluconazole preparations in healthy thai volunteers.

AIM: To determine the bioequivalence of two oral formulations of generic fluconazole in twelve healthy Thai volunteers. SUBJECTS, MATERIALS AND METHODS: The test preparation was Flucozole (Siam Bheasach, Thailand) and the reference was Diflucan (Pfizer Inc.). The two products were administered as 200 mg single oral doses in a two-period crossover design with a two-week washout period. After drug administration, serial blood samples were collected over a period of 72 hours. Serum fluconazole concentrations were determined by HPLC, and the pharmacokinetic parameters were analyzed by non-compartmental analysis. RESULTS: The time to reach the maximal concentration (Tmax, hour) of Flucozole (1.18 +/- 0.56) was statistically faster than that of Diflulan (1.59 +/- 0.54). The 90% confidence intervals of the AUC(0 - infinity) ratio and the Cmax, ratio muT/muR for Flucozole/Diflucan were 0.97 - 1.20 and 1.01 - 1.26, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25 and 0.7 - 1.43 for the ratio of the average AUC(0 - infinity) and Cmax, respectively. CONCLUSION: Thus, our study demonstrated the bioequivalence of Flucozole and Diflucan with respect to the rate (Cmax) and extent of absorption (AUC(0 - infinity).

Pharmacokinetics and bioequivalence testing of generic ondansetron preparations in healthy Thai male volunteers.

SUBJECTS, MATERIAL AND METHODS: Pharmacokinetics and bioequivalence of oral preparations of generic ondansetron were investigated in healthy Thai males. The test preparations were Vomitron 8 and Vomitron 4, the reference was Zofran. The three products were administered as an 8 mg single oral dose, in a three-period four-sequence cross-over design with one-week washout period. An intravenous 8 mg Zofran was administered on the forth visit. Plasma ondansetron concentrations were determined by HPLC and the pharmacokinetic parameters were analyzed by non-compartmental analysis. RESULTS: Following i.v. ondansetron, the mean values of its elimination half-life, its plasma clearance, and its volume of distribution were 4.5 hours, 398 ml/min, and 130 liters, respectively. Its oral bioavailability averaged 67%, and the elimination half-life after oral administration was 5.6 hours. The time to reach the maximal concentration (Tmax, hour) of Zofran (1.21 +/- 0.26) was statistically faster than that of Vomitron 8 (1.33 +/- 0.54) and Vomitron 4 (1.46 +/- 0.50). The 90% confidence intervals of the AUC0-infinity and Cmax ratios muT/muR for (Vomitron 8/Zofran) were 0.88 - 1.12 and 0. 85 - 1.08, respectively. Similarly the 90% CI of the-AUC0-infinity and Cmax ratios for (Vomitron 4/Zofran) were 0.96 - 1.17 and 1.01 - 1.19, respectively. CONCLUSION: These values were within the acceptable range of 0.80 - 1.25, thus our study demonstrated the bioequivalence of Vomitron and Zofran with respect to the rate (Cmax) and extent of absorption (AUC0-infinity).

Bioequivalence study of generic atenolol tablets in healthy Thai volunteers.

Two preparations of 50 mg and 100 mg atenolol tablets were evaluated for their bioequivalence in twelve healthy Thai subjects (Prenolol, Berlin Pharmaceutical Industry, as the test formulations vs Tenormin, Zeneca Limited, as the reference formulations). A single oral dose of each preparation was administered in a randomized two-way crossover design, starting from either 50 mg of Prenolol vs Tenormin, thereafter, either 100 mg of Prenolol vs Tenormin. The washout period between each treatment was one week. Atenolol plasma concentrations were determined by the HPLC technique with fluorometric detection. Pharmacokinetic parameters were analyzed by the noncompartmental pharmacokinetic method using TOPFIT. The means and parametric 90 per cent confidence intervals of the ratio [Prenolol/Tenormin] of AUC0-infinity and Cmax were 1.16 (1.05-1.27) and 1.23 (1.07-1.38) for 50 mg preparations and 1.10 (1.00-1.20) and 1.13 (0.95-1.31) for 100 mg preparations, respectively. These values were well within the acceptable bioequivalence ranges. The mean differences of Tmax [Prenolol-Tenormin] were less than 20 per cent for both 50 mg and 100 mg preparations. Hence, Prenolol and Tenormin were bioequivalent with respect to the rate and extent of absorption.

Pharmacokinetics and bioavailability studies of generic ondansetron, and the innovator preparation, in healthy Thai male volunteers.

The pharmacokinetics and bioequivalence of two oral formulations of ondansetron were evaluated; Zetron (Biolab Pharmaceutical, Bangkok, Thailand), as the test formulation and Zofran (Glaxo Wellcome Operations, Greenford, UK), as the reference formulation. The two products were administered as a single oral dose of 8 mg according to a randomized two-way crossover design to 12 healthy Thai male volunteers. The washout period between treatment was 1 week. Ondansetron plasma concentrations were measured using HPLC. The oral bioavailability of ondansetron averaged 67 per cent and the elimination half-life after oral administration was 5.6 hours. The means and parametric 90 per cent CI of the ratios of Cmax and AUC 0-alpha [mu Zetron (Test)/mu Zofran (Reference)] were 0.95 (0.84-1.07) and 0.94 (0.80-1.10), respectively. These values were well within the bioequivalence range of 0.8-1.25 as established by the US-FDA. The mean difference of Tmax (Test-Reference) was approximately 20 per cent. Thus, our study demonstrated bioequivalence of the two products (Zetron and Zofran) regarding the rate and extent of absorption.