Bioequivalence and Pharmacokinetics Study of Two Zidovudine/Lamivudine Tablets in Chinese Healthy Volunteers.

Zidovudine/lamivudine tablets are nucleoside reverse transcriptase inhibitors that are used to treat human immunodeficiency virus. The objective of this study was to investigate the bioequivalence and pharmacokinetics (PKs) of test and reference preparations of zidovudine/lamivudine tablets in healthy Chinese subjects. We designed a randomized, open, single-center, single-dose, 2-crossover experiment with a 7-day washout period involving 20 healthy subjects. The subjects were given a single dose of the test or reference preparation after fasting overnight for 10 hours. Blood samples were subsequently collected at scheduled time points from 0 hour (preadministration) up to 24 hours postadministration. The plasma concentrations of zidovudine and lamivudine were determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Analysis of variance (ANOVA) was used to compare differences in the mean values of key PK parameters between the 2 preparations. Bioequivalence was evaluated by 2 one-sided t-tests and 90% confidence intervals (CIs) of the geometric mean ratio (GMR). In total, 19 of the 20 subjects completed the trial. Based on the analysis of PK parameters, the relative bioavailability of zidovudine and lamivudine was 101.1% ± 2.0% and 100.3% ± 1.5%, respectively. ANOVA found no significant difference in primary PK parameters when compared between the 2 formulations, and the 90% CIs of the GMR of the 2 formulations were within the bioequivalence margins of 80%-125%. No serious adverse events occurred. Thus, we confirmed that the 2 preparations were bioequivalent in healthy Chinese volunteers. Our analysis demonstrated that both products showed good tolerance in all subjects.

A UPLC-MS/MS method for simultaneous quantification of sildenafil and N-desmethyl sildenafil applied in pharmacokinetic and bioequivalence studies in a Chinese population.

OBJECTIVE: To evaluate the pharmacokinetic parameters and bioequivalence of two sildenafil tablets (20 mg) in healthy Chinese subjects. MATERIALS AND METHODS: A random, crossover, self-control design was used. 20 healthy subjects including males and females were randomized into two groups. A single oral dose of the trial or reference preparation was given to the two groups of subjects after an overnight fast of 10 hours. Blood samples were taken at scheduled time points. Plasma concentrations of sildenafil and N-desmethyl sildenafil were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). ANOVA was used to check the difference of the mean values of the pharmacokinetic parameters between the two preparations. Bioequivalence was determined by two one-sided t-tests and 90% confidence intervals. RESULTS: The quantitative range of sildenafil and N-desmethyl sildenafil was 2.000 - 200.0 ng/mL and 0.800 - 80.00 ng/mL, respectively. Plasma samples were stable, and there was no mutual interference between the analyte and internal standard. With the 90% confidence limit, the trial preparations AUC0→t and Cmax fall within 80.00 - 125.00% of the reference preparation's AUC0→t and Cmax. The tmax of sildenafil and N-desmethyl sildenafil was ~ 0.9 hours and 1 hour, and the T1/2 was 2.4 hours and 3.7 hours, respectively. The relative bioavailability of sildenafil and N-desmethyl sildenafil was 99.28 ± 3.30% and 99.20 ± 3.39%. No significant difference was found in every factor between the trial preparation and the reference preparation. CONCLUSION: The UPLC-MS/MS method was successfully established to evaluate the pharmacokinetic parameters of sildenafil in healthy Chinese subjects. The trial preparation was bioequivalent to the reference preparation.

[Research on Risk Control of Upgraded Design and Development Changes of Laser Treatment Equipment after Registration].

This paper analyzes the causes and risks of common design and development changes of laser treatment equipment, studies the changes of key components and their corresponding control measures, forms the identification method of design changes of laser treatment equipment, and gives suggestions on how to deal with design and development changes, so as to provide references for inspectors during on-site inspection.