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背景:先前的一个利福平(RMP)监测性研究显示,结核病(TB)患者在使用常规的3药固定剂量复方制剂(3FDC)治疗时,RMP浓度很低。因此,我们对该制剂的生物利用度进行研究。目的:利用健康志愿者研究墨西哥卫生保健系统中常规使用的3FDC制剂相对于参比制剂的RMP相对生物利用度。设计:两周期、两序列的交叉研究。结果:受试制剂和参比制剂的药代动力学参数均值如下:达峰浓度(Cmax)分别为3.13±2.01μg/ml和9.95±2.66μg/ml;对于血药浓度-时间曲线下面积(AUC),零到最后实测浓度的AUC(AUC0-12 h)分别为15.51±9.77μg.h/ml和58.03±16.1μg.h/ml,零到无限大时间的AUC(AUC0-∞)分别为17.92±10.66μg.h/ml和68.43±22.39μg.h/ml。Cmax的受试/参比均值比(90%CI)为25.36%(17.33~37.10);AUC0-12 h为21.25%(14.61~30.89);AUC0-∞为22.08%(15.44~31.56)。这些结果不符合生物等效性标准。结论:受试制剂与参比制剂相比,显示吸收延迟和RMP生物利用度明显偏低。含RMP的常规制剂只有在其生物利用度评估后可确保与参比制剂互换,并确保在其使用过程中不出现RMP浓度明显偏低的危险时,才能应用。
BACKGROUND: A previous RMP monitoring study showed that patients with tuberculosis (TB) had low RMP concentrations when treated with the conventional 3-dose fixed-dose combination (3FDC). Therefore, we investigated the bioavailability of this preparation. OBJECTIVE: To study the relative bioavailability of RMP of the 3FDC formulations routinely used in the Mexican health care system relative to the reference formulation using healthy volunteers. Design: Two-Cycle, Two-Series Cross-Research. Results: The mean pharmacokinetic parameters of the test and reference preparations were as follows: the peak concentrations (Cmax) were 3.13 ± 2.01μg / ml and 9.95 ± 2.66μg / ml, respectively; for the area under the plasma concentration-time curve AUC), AUC (AUC0-12 h) from zero to the last measured concentration were 15.51 ± 9.77μg.h / ml and 58.03 ± 16.1μg.h / ml respectively. The AUC (AUC0-∞) from zero to infinity were 17.92 ± 10.66 μg.h / ml and 68.43 ± 22.39 μg.h / ml. The Cmax test-reference mean ratio (90% CI) was 25.36% (17.33-37.10); AUC0-12 h was 21.25% (14.61-30.89); AUC0-∞ was 22.08% (15.44-31.56). These results do not meet the bioequivalence criteria. CONCLUSIONS: Compared with the reference formulation, the test formulation showed delayed absorption and significantly lower RMP bioavailability. RMP-containing conventional preparations can only be used if their bioavailability assessment ensures interchangeability with reference preparations and ensures that they do not present a significant risk of a low RMP concentration during their use.