生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence Study of Two 30 Mg Tolvaptan Tablets Formulations in Healthy Chinese under Fed Condition

Xiaogao Zhang and Shengjun Zhang

Objective: The purpose of this study was to compare the bioavailability between the two 30 mg tolvaptan tablets formulations and to evaluate the bioequivalence of Reference and Test formulations of tolvaptan tablets 30 mg in healthy adult male and female subjects under fed condition. Method: 50 healthy Chinese male and female subjects were enrolled in a single-center, randomized, open-label, single-dose, two-treatment, two-sequence, two-period, crossover study. The plasma of tolvaptan were determined by a validated LC- MS/MS method. The bioequivalence of Test and Reference will be determined based on AUC0-t, AUC0‑inf and Cmax of tolvaptan in plasma. Results: All the 50 subjects completed the study and the main pharmacokinetic parameters for test and reference preparations were as follows: Cmax were 308.8 ± 108.8 and 339.9 ± 114.3 ng/mL, tmax were 2.670 (1.0–6.0) and 2.330 (1.0–6.0) h, AUC0-48 were 1832 ± 781.8 and 1702 ± 616.2 ng∙h/ml, AUC0-inf were 1848 ± 785.2 and 1720 ± 616.7 ng∙h/ml, t1/2 were 4.742 ± 1.129 and 4.608 ± 1.120 h. The 90% confidence intervals (CIs) of Cmax, AUC0-48 and AUC0-inf on the ratio of test to reference formulation were 82.83%-97.61%, 99.55%-112.91% and 99.44%-112.66%, respectively. The results of two one-side t test and variance analysis showed that there was no significant difference between the main parameters of the two preparations (P>0.05). Conclusion: This study shows that two tolvaptan tablets 30 mg preparations are bioequivalent in Chinese adult healthy volunteers under fed condition.