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摘要
Background: This study aimed to test the hypothesis that paediatric fixed-dose combination granule for reconstitution (comprising lamivudine/zidovudine/nevirapine 30/60/50 mg per 5 ml) as a test product is bioequivalent to the coadministered single entities of the reference products. Fixed-dose combination antiretroviral therapy provides adequate suppression of HIV-1 replication, provides barrier to the development of resistance, simplifies dosage regimen and improves adherence.
Methods: An open label, randomized, two-way crossover study was conducted on 24 healthy adults under fasted conditions, with a washout period of 14 days between treatments. A total of 15 blood samples were collected before dosing and up to 96 h post dosing. The drugs were extracted from plasma and analysed using a validated high performance liquid chromatography - ultraviolet method. Non-compartmental pharmacokinetic (PK) analysis was performed to obtain the PK parameters, maximum plasma concentration (C-max), area under curve of plasma concentration- time curves from time zero to last measurable concentration (AUC(0-t)) and area under curve extrapolated to infinity (AUC(0-infinity)). ANOVA test was performed to determine the effect of model factors on the PK parameters. The two one-sided t-tests were performed on the log-transformed data to determine the 90% CI for the ratio of test to reference PK parameters.
Results: The drugs were well tolerated and safe, with minimal adverse events. The ANOVA test indicated the absence of any significant effects (P>0.05) due to the model parameters. The 90% CI for the geometric mean ratio of test/ reference for C-max, AUC(0-t) and AUC(0-infinity) for lamivudine, zidovudine and nevirapine were within the 80-125% bioequivalence limits.
Conclusions: This single-dose randomized study found that the test and reference products met the criteria for bioequivalence in the fasting healthy adult volunteers.
- 出版日期2013
