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® (General Pharmaceutical Ltd., Bangladesh) (Test formulation) and Zithromax® (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 noncompartmental 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 Cmax; 4.83(1.03), 4.83(1.03) h for tmax; 5,646.29 (912.19), 6,293.30 (966.76) h×ng/ml for AUC0-120; and 6,307.50 (863.40), 7,022.54 (961.28) h×ng/ml for AUC0-∞, respectively. The mean t1/2 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 Cmax, AUC0-120, AUC0-∞ and AUMC0-120. The 90% confidence intervals of the test/ reference mean ratios of the ln-transformed Cmax, AUC0-120 and AUC0-∞ 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.

Comparative pharmacokinetic and relative bioavailability study of coated and uncoated azithromycin powder for suspension in healthy Bangladeshi male volunteers.

Azithromycin (AZT; CAS 83905-01-5) is an efficient antibiotic and is widely prescribed in Bangladesh. The taste of uncoated AZT suspension is bitter. Although several taste masked oral suspensions of AZT are available in Bangladesh, information regarding the bioavailability of these formulations in Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of two oral formulation of AZT (200 mg/5 ml) suspensions, the uncoated reference product and coated test product (Tridosil 200 mg/5 ml) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi male volunteers. A randomized, single-dose, two-way cross-over, open-label pharmacokinetic study was conducted in 24 healthy male volunteers after administration of a single dose of 500 mg AZT suspension under fasting condition following a washout period of three weeks. Blood samples were collected in different time intervals and analyzed for serum AZT concentration using a validated LC/MS/MS method. The pharmacokinetic parameters were determined by the non-compartmental method. From serum data, the obtained values for test and reference products were 383.21 +/- 11.59 and 432.28 +/- 7.22 ng/ ml for Cmax; 5677.47 +/- 1229.53 and 6144.56 +/- 1098.70 h x ng/ml for AUC(0-120); and 6085.29 +/- 1267.53 and 6694.15 +/- 1222.50 h x ng/ml for AUC(0-infinity), respectively. On analysis of variance, no period or sequence effects were observed for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax and AUMC(0-infinity). The 90% confidence intervals of the test formulation/reference mean ratios of the Intransformed Cmax, AUC(0-120) and AUC(0-infinity) mean values were found to be 87.89% to 89.36%, 87.96% to 95.71% and 86.77% to 94.29% respectively. In this single-dose study of AZT, it was found that the test formulation met the regulatory criteria for bioequivalence to the reference suspension formulation.