Pharmacokinetics and Bioequivalence Study of Two Indapamide Formulations after Single-dose Administration in Healthy Chinese Male Volunteers

Abstract

The pharmacokinetics and relative bioavailability/bioequivalence of 2 formulations of indapamide were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study design with a wash-out phase of 7 days. Blood samples for pharmacokinetic profiling were taken up to 84 h post-dose, and indapamide concentrations in plasma were determined by a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Based on the plasma concentration-time data of each individual in each period, pharmacokinetic parameters, C_max, AUC_0–τ, AUC_0–∞ and t_1/2, were calculated by non-compartmental analysis. Pharmacokinetic parameters for test and reference formulations were analyzed statistically to assess bioequivalence of the 2 formulations. The values of C_max, T_max, t_1/2, AUC_0–τ, AUC_0–∞ for test and reference formulations were 49.53±5.53 and 47.79±4.68 ng/mL, 1.9±0.6 and 2.0±0.5 h, 22.49±5.93 and 23.23±4.48 h, 859.51±160.92 and 840.90±170.62 ng · h/mL, 934.35±190.60 and 919.52±179.74 ng · h/mL, respectively. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were within the accepted range of 80–125%. It showed that the 2 formulations of indapamide were bioequivalent. Both preparations were well tolerated and no adverse reactions were found throughout the study.

Key words

indapamide - pharmacokinetics - bioequivalence - healthy volunteers - HPLC-MS - human plasma

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