阿奇霉素颗粒剂和片剂的人体相对生物利用度及生物等效性评价

目的研究阿奇霉素颗粒剂和片剂在健康人体内的药物动力学及相对生物利用度,为临床合理用药提供依据。方法采用三周期三交叉试验设计,利用建立的液相色谱-串联质谱法测定24名健康男性受试者口服含阿奇霉素0.5 g的阿奇霉素颗粒(受试制剂Ⅰ)、阿奇霉素片A(受试制剂Ⅱ)及阿奇霉素片B(参比制剂)后不同时刻血浆中阿奇霉素的质量浓度,同时绘制血药质量浓度-时间曲线并计算主要药物动力学参数。结果阿奇霉素颗粒、阿奇霉素片A、B血浆中阿奇霉素的tmax分别为(1.9±0.6)、(1.9±0.7)、(1.8±0.6)h,ρmax分别为(441.0±129.5)、(421.7±142.8)、(426.2±128.1)μg.L-1,t1/2分别为(48.0±10.7)、(44.8±8.0)、(45.6±9.8)h,AUC0-t分别为(4 564.6±1 312.0)、(4 743.1±1 616.1)、(4 654.6±1 489.4)μg.h.L-1,AUC0-∞分别为(5 224.6±1 529.7)、(5 373.4±1 854.7)、(5 278.7±1 675.9)μg.h.L-1。以AUC0-t计算,阿奇霉素颗粒剂及片剂的相对生物利用度分别为(99.7±14.0)%和(101.8±13.8)%。结论双单侧检验结果证明,阿奇霉素颗粒及阿奇霉素片A与阿奇霉素片B具有生物等效性。

Assessment of relative bioavailability and bioequivalence of azithromycin granules and tablets

0bjective To study the pharmacokinetics and relative bioavailability of azithromycin granules and tablets. Methods A liquid chromatography-tandem mass spectrometry （LC-MS-MS） method was developed to determine plasma concentrations of azithromycin in 24 healthy Chinese male volunteers following a 0.5 g dose of azithromycin granules (test formulationⅠ), azithromycin tablets A (test formulationⅡ) and azithromycin tablets B(reference formulation) with three cross-over design, the blood concentration-time curves were ploted and the main pharmacokinetic parameters were calculated. Results The main pharmacokinetic parameters of testⅠ, testⅡand reference formulation were: tmax(1.9±0.6), (1.9 ±0.7) , (1.8 ± 0.6) h; ρmax(441.0±129.5), (421.7±142.8), (426.2±128.1) mg·L-1; t1/2(48.0±10.7), (44.8±8.0), (45.6±9.8) h; AUC0-t(4 564.6±1 312.0), (4 743.1±1 616.1), (4 654.6±1 489.4) mg·h·L-1; AUC0-¥(5 224.6±1 529.7), (5 373.4±1 854.7), (5 278.7±1 675.9) mg·h·L-1, respectively. According to AUC0-t, the relative bioavailability of azithromycin granules and tablets were (99.7±14.0) % and (101.8±13.8) %. Conclusion According to the two one–side tests, azithromycin of tests and reference formulations are bioequivalent．