A fully replicated crossover bioequivalence study of mycophenolate mofetil capsules in Chinese healthy male subjects under fasting and fed conditions / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of the test and reference formulations of mycophenolate mofetil capsule in Chinese healthy male subjects under fasting and fed conditions. METHODS: This was a 2-treatment, 2-sequence, 4-period, fully replicated crossover study that included 80 Chinese healthy male subjects (40 subjects in the fasting group and 40 subjects in the fed group, respectively). Subjects were assigned to receive a single oral administration of the test or reference formulation at a dose of 0.25 g in each period. The plasma concentration of mycophenolate mofetil (MMF) and metabolite mycophenolic acid (MPA) were analyhed by LC-MS/MS. The major pharmacokinetic parameters of MMF and MPA were calculated using non-compartmental analysis by WinNonlin 8.0. The statistical analysis was performed by SAS 9.4. Average bioequivalence (ABE) analysis was applied where it has been demonstrated that the within-subject standard deviation of the reference formulation (S

Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects

The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-∞ of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.

New software for carrying out data analysis of bioavailability and bioequivalence testing / 中国临床药理学与治疗学

Generic drug products (test products: drug A, B...) are bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar. Bioavailability is usually expressed by following pharmacokinetic parameters: the area under plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) and the time of maximum plasma concentration (tmax). This paper used a two period crossover bioequivalence study to develop convenient, friendly user interface software, BA&BE Analysis to statistically process data in clinical pharmacology studies and other areas. The method involves user input of data for analysis into a grid format, setting variables and parameters, followed by one-way analysis of variance (ANOVA), bioavailability and bioequivalence analysis of the data. The software developed in the present study should help scientists to carry out data analysis of bioavailability and bioequivalence testing quickly and easily.