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.

Comparative studies of quality and bioavailability of methotrexate in Thai patients with rheumatoid arthritis.

The bioavailability of the two generic methotrexate oral preparations (Emtrexate, Pharmachemie Company, Holland and Methotrexate Remedica, Remedica, Cyprus as the test preparations), were compared to the innovator (Methotrexate Lederle, Lederle, U.S.A. as the reference) in 10 patients with rheumatoid arthritis. A single 7.5 mg oral dose of each preparation was given to the subjects in a randomized, double-blind, three-period crossover design with a 1 week washout period. Serum methotrexate concentrations were determined by using Fluorescence Polarization Immunoassay (Abbott TDx). No significant differences in pharmacokinetic parameters (AUC, Cmax, and Tmax) were observed between the test and reference preparations. The mean and 90 per cent CI of the ratio Emtrexate/Methotrexate Lederle and Methotrexate Remedica/Methotrexate Lederle of the Cmax, AUC0-8, and AUC0-alpha were 0.93 (0.87-1.00), 0.9 (0.82-0.98), 0.88 (0.79-0.99) and 0.97 (0.93-1.02), 0.95 (0.90-0.99), 0.94 (0.86-1.02), respectively. These values were well within the acceptable bioequivalence range of 0.8-1.25. The mean and 90 per cent CI of Tmax difference between Emtrexate-Methotrexate Lederle and Methotrexate Remedica-Methotrexate Lederle also overlapped the stipulated bioequivalence range of the Tmax differences of +/- 0.25 hour. Thus, Emtrexate and Methotrexate Remedica were considered bioequivalent to the reference Methotrexate Lederle regarding the rate of absorption and the extent of absorption.

The comparative bioavailability of a generic and the innovator fluconazole preparations in healthy Thai volunteers.

We studied the pharmacokinetics and compared the oral bioavailability of the "generic" (Biozole, Biolab Company, Thailand) and the "innovator" (Diflucan, Pfizer Incorporation, U.S.A.) fluconazole preparations in 12 healthy Thai volunteers. A 200 mg single oral dose of each preparation was given to the subjects in a randomized double-blind 2-period crossover design with 2 weeks washout period. Blood samples were collected just before and at 0.5, 1, 2, 2.5, 3, 4, 24, 48, 56 and 72 hours after drug administration. Serum fluconazole concentrations were determined by using high performance liquid chromatography. Individual concentration-time profiles and the pharmacokinetic parameters were analyzed by the noncompartmental pharmacokinetic method [TOPFIT, a pharmacokinetic data analysis program]. The pharmacokinetic parameters (Tmax, Cmax, Vd, Cl) of fluconazole in Thai healthy volunteers were comparable to those values observed in Caucasian subjects. The relative bioavailability of the generic Biozole was 102.38 +/- 9.79 per cent of Diflucan. The means and 90 per cent confidence intervals (90% CI) of the [Biozole/Diflucan] ratio of AUC0-72, AUC0-inf and Cmax were 1.02 (0.98-1.06), 0.99 (0.95-1.03) and 1.13 (1.03-1.25), respectively. These values were well within the acceptable bioequivalence ranges of 0.8-1.25 proposed by the US FDA. The means and 90 per cent CI of Tmax differences [Biozole-Diflucan] were -0.46 [(-1.03)-(0.12)]. This value was outside the stipulated bioequivalence range of +/- 0.41 h (+/- 20% of the Tmax of the reference formulation). Nevertheless, the Tmax difference was not expected to be related to the differences in safety and efficacy of the drug. Hence, Biozole and Diflucan were bioequivalent with respect to the extent of absorption (AUC), and the Cmax, and could be used interchangeably.