In vivo bioequivalence of oral antidiabetic agents: pioglitazone tablets.

摘要

The study was designed to evaluate the bioequivalence of two pioglitazone (CAS 112529-15-4) formulations. The trial was performed in 26 healthy male volunteers with the aim of comparing a new generic product (tablets containing 30 mg pioglit-azone hydrochloride, test) with the originator product (reference). The trial was performed according to an open, crossover design in one study centre. In each of the two study periods (separated by a wash-out of 14 days) a single oral dose of 30 mg (test or reference) formulation was administered. Blood samples were taken up to 120 h post dose, the plasma was separated and the concentrations of pioglitazone and its principal active metabolite hydroxypioglitazone were determined by LC-MS-MS method. AUC0-inf, AUC0-t, Cmax, and Tmax were calculated for both formulations. The mean Cmax of pioglitazone ranged between 1.01 microg/mL and 1.05 microg/mL, while the mean AUC0-inf and AUC0-t ranged between 10.89 microg x h/mL and 10.98 microg x h/mL as well as between 10.56 microg x h/mL and 10.62 microg x h/mL for the test and reference formulations, respectively. The median Tmax for the test tablets was 1.50 h and for the reference was 1.75 h. The ratios test/reference formulation for AUC0-inf, AUC0-t and Cmax were 99.70%, 100.13% and 99.17%, respectively. Furthermore, the 90% geometric confidence intervals of the mean ratio of In-transformed AUC0-inf were narrow and symmetrical around 100%, i.e. 90.59% to 109.72%, for AUC0-t, 90.69% to 110.55%, whereas for Cmax they were 87.52% to 112.37%. As in the case of pioglitazone, mean values of the principal bioequivalence parameters of hydroxypioglitazone did not differ significantly after administration of the test and reference formulations. In the light of the present study it can be concluded that the two evaluated pioglitazone formulations, i.e. test formulation of pioglitazone hydrochloride and reference formulation, are bioequivalent in terms of the rate and extent of absorption.