Comparative pharmacokinetic and bioequivalence study of azithromycin 500 mg tablet in healthy Bangladeshi volunteers

Objective: Although several generic oral formulations of azithromycin (AZT; CAS 83905-01-5) are available in Bangladesh, information regarding the bioavailability of these formulations in the Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of 2 formulations of AZT 500 mg tablet, namely Azomac (R) (General Pharmaceutical Ltd., Bangladesh) (Test formulation) and Zithromax (R) (Pfizer, Rome, Italy) (Reference product) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi volunteers. Materials and methods: A randomized, single-dose, two-way, cross-over, open-label pharmacokinetic study was performed in 24 healthy volunteers after administration of single dose of AZT 500 mg tablet under fasting condition following a washout period of 3 weeks. Blood samples were collected at pre-determined time points and analyzed for serum AZT concentration using a validated liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were determined by a non-compartmental method. Results: From serum data, the obtained values given as mean (SD) for test and reference products were 382.41 (21.96), 392.31 (18.77) ng/ml for C-max; 4.83(1.03), 4.83(1.03) h for t(max); 5,646.29 (912.19), 6,293.30 (966.76) hxng/ml for AUC(0-120), and 6,307.50 (863.40), 7,022.54 (961.28) hxng/ml for AUC(0-infinity), respectively. The mean t(1/2) was 41.44 (7.01), 41.16 (6.38) h for Test formulation and Reference product, respectively. The analysis of variance revealed no period or sequence effect for any pharmacokinetic property; however, a significant formulation effect was observed for C-max, AUC(0-120), AUC(0-infinity), and AUMC(0-120). The 90% confidence intervals of the test/reference mean ratios of the In-transformed C-max, AUC(0-120) and AUC(0-infinity) were 87.89 - 89.36%, 87.40 - 91.70% and 87.47 - 92.07%, respectively, which fell within the predetermined FDA bioequivalence range. Conclusion: It can be concluded that the test formulation met the regulatory criteria for bioequivalence to the Reference tablet formulation in terms of both rate and extent of absorption.