Bioequivalence of allopurinol and its metabolite oxipurinol in two tablet formulations.

Abstract

To test for the bioequivalence of two allopurinol 300 mg tablet formulations (generic allopurinol (Normon) and Zyloric tablets). A single dose study was carried out in 24 healthy volunteers with a two-sequence, crossover block-randomized design. Blood samples were taken prior to each administration and at 19 points within 72 h after the dose. Plasma concentrations of allopurinol and oxypurinol were determined by HPLC. The pharmacokinetic parameters Cmax and Tmax were obtained directly from plasma allopurinol and oxypurinol concentrations. ke was estimated by log-linear regression and AUC was calculated by the linear trapezoidal rule for both allopurinol and oxypurinol. The pharmacokinetic parameters AUC and Cmax were tested for equivalence after log-transformation of data. Differences of Tmax were evaluated by a non-parametric test. The 90% standard confidence intervals of the mean values for the test/reference ratios were for AUC and for Cmax, within the acceptable bioequivalence limits of 0.80-1.25 for both allopurinol and oxypurinol. The two formulations are bioequivalent and therefore interchangeable.