Bioavailability and Bioequivalence of Allopurinol in Two Tablet Formulations
Saied M. I. Al-Dalaen*
, Abdul-Wahab R. Hamad, Fawaz Al-Saraireh, Rawan Nayef Alkaraki, Mousa Khames Mezel Magarbehand Fahil M. AbidCollege of Pharmacy, Mutah University, AlKarak, Jordan.
Corresponding Author E-mail : wahabhamad2004@yahoo.com
Abstract: Background: Allopurinol is an effective inhibitor of the enzyme xanthine oxidase, use for decreasing the blood concentrations of urate and, therefore, to decrease the quantity of repeated assaults of gout. Allopurinol is metabolized to oxipurinol, and hypouricaemic efficacy of allopurinol is due very in large part to this metabolite. Objective: To study and compare the bioavailability and bioequivalence of two allopurinol 300 mg tablet formulations, test drug (Hyporic tablet, SDI) and reference drug (Zyloric tablets, GlaxoWellcome). Method: A single dose study was carried out in 20 healthy volunteers with a two-sequence, crossover block-randomized design. Blood samples were taken prior to each administration and at 0 time and post administration at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 9.0 and 12.0 hours after the dose. Standards and plasma concentrations of allopurinol were determined by HPLC. The pharmacokinetic parameters; maximum concentration (C-max) and maximum time (T-max) were obtained directly from plasma allopurinol concentrations for both reference and test drugs. Area under curve (AUC) was calculated by the linear trapezoidal rule for both Hyporic tablet and Zyloric tablet. Results: The pharmacokinetic parameters AUC and C-max were tried for proportional after log-transformation of data. The maximum concentrations (C-max) of allopurinol for both 300mg hyporic and 300mg zyloric tablets were 29.8±3.372 and 30.6±2.507 mg at maximum time of 1.5 hours for both formulation, it was not significantly differences. The AUC for both test and reference tablets were 90.525±11.677 and 92.817±9.752, respectively. Allopurinol has a plasma half-life of about 2.0±0.141 and 2.1±0.148 hours Hyporic drug as a test and Zyloric drug as a reference, respectively. The 90% standard confidence intervals of the mean values for the test/reference ratios were for AUC and for C-max, within the acceptable bioequivalence limits of 0.80-1.25 for both Reference and Test tablets. Conclusion: The two formulations are bioequivalent for Hyporic tablet (SDI) and Zyloric tablet (GlaxoWellcome). The results of all the applied statistical test suggest that Hyporic and Zyloric tablets can be considered as bioequivalent preparations and therefore interchangeable.
Keywords: Allopurinol; Bioequivalence; Bioequivalence Back to TOC