Ahmed Maizbha Uddin, Islam Mohammad Safiqul, Shohag Hasanuzzaman, Karim Rubaba, Mostofa A G M, Bhuiyan Nurul Huda, Rahim Matiur, Hasnat Abul
Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Bangladesh.
Int J Clin Pharmacol Ther. 2012 Jun;50(6):452-8. doi: 10.5414/cp201616.
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.
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.
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.
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.
虽然孟加拉国已有几种阿奇霉素（AZT；化学物质登记号83905-01-5）的普通口服制剂，但尚无这些制剂在孟加拉国人群中的生物利用度信息。本研究的目的是比较两种500毫克AZT片剂制剂，即Azomac®（孟加拉国通用制药有限公司）（受试制剂）和Zithromax®（意大利罗马辉瑞公司）（参比产品）的相对生物利用度及其他药代动力学特性，并评估这些制剂在孟加拉国志愿者中是否符合美国食品药品监督管理局（FDA）关于生物等效性的标准。
在24名健康志愿者中进行了一项随机、单剂量、双向、交叉、开放标签的药代动力学研究，在经过3周的洗脱期后，于禁食条件下给予单剂量500毫克AZT片剂。在预定时间点采集血样，采用经过验证的液相色谱-串联质谱法分析血清中AZT浓度。药代动力学参数通过非房室方法确定。
从血清数据来看，受试制剂和参比产品的均值（标准差）如下：Cmax分别为382.41（21.96）、392.31（18.77）纳克/毫升；tmax分别为4.83（1.03）、4.83（1.03）小时；AUC0-120分别为5,646.29（912.19）、6,293.30（966.76）小时×纳克/毫升；AUC0-∞分别为6,307.50（863.40）、7,022.54（961.28）小时×纳克/毫升。受试制剂和参比产品的平均t1/2分别为41.44（7.01）、41.16（6.38）小时。方差分析显示，任何药代动力学特性均无周期或序列效应；然而，观察到Cmax、AUC0-120、AUC0-∞和AUMC0-120存在显著的制剂效应。ln转换后的Cmax、AUC0-120和AUC0-∞的受试/参比均值比90%置信区间分别为87.89 - 89.36%、87.40 - 91.70%和87.47 - 92.07%，均落在预定的FDA生物等效性范围内。
可以得出结论，受试制剂在吸收速率和程度方面均符合与参比片剂制剂生物等效的监管标准。
