利福平与异烟肼固定剂量复方制剂和单药制剂的相对生物利用度

Comparative bioavailability of rifampicin and isoniazid in fixed-dose combinations and single-drug formulations.

作者信息

Hao L-H, Guo S-C, Liu C-C, Zhu H, Wang B, Fu L, Chen M-T, Zhou L, Chi J-Y, Yang W, Nie W-J, Lu Y

机构信息

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.

National Center for Tuberculosis Control and Prevention, Chinese Centers for Disease Control and Prevention, Beijing, China.

出版信息

Int J Tuberc Lung Dis. 2014 Dec;18(12):1505-12. doi: 10.5588/ijtld.13.0647.

DOI:10.5588/ijtld.13.0647

PMID:25517820

Abstract

SETTING

The bioavailability of rifampicin (RMP) decreases by ∼30% on interaction with isoniazid (INH) in stomach acid conditions, which can result in the development of drug resistance and treatment failure.

OBJECTIVE

To compare the bioavailability in healthy volunteers of five anti-tuberculosis fixed-drug combinations (FDCs) used in China (formulations A-E) containing RMP and INH against single-drug formulations taken as reference.

DESIGN

Two- or three-period, two- or three-sequence crossover study of drugs.

RESULT

Only RMP formulation E passed the bioequivalence criteria, with 90% confidence intervals for the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax of respectively 89.9-103.7, 89.6-102.2 and 87.7-107.9. For INH, formulations A, B, C and D passed the bioequivalence test, but not product E, where the 90%CIs of the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax were respectively 85.2-100.7, 85.2-100.7 and 73.8-100.9.

CONCLUSION

According to the results of the bioequivalence analysis carried out in this study, RMP formulations A, B, C and D were not within the acceptable range and only formulation E passed the bioequivalence criteria of 80-125%. In comparison, four-test INH formulations (A, B, C and D) were bioequivalent to the corresponding single-drug formulation, while product E failed in the bioequivalence criteria.

摘要

背景

在胃酸环境中，利福平（RMP）与异烟肼（INH）相互作用后，其生物利用度会降低约30%，这可能导致耐药性的产生和治疗失败。

目的

比较中国使用的五种含RMP和INH的抗结核固定剂量复方制剂（FDC，即制剂A - E）与作为对照的单药制剂在健康志愿者中的生物利用度。

设计

药物的两期或三期、两序列或三序列交叉研究。

结果

仅RMP制剂E符合生物等效性标准，AUC₀₋₂₄、AUC₀₋∞和Cmax对数转换比值的90%置信区间分别为89.9 - 103.7、89.6 - 102.2和87.7 - 107.9。对于INH，制剂A、B、C和D通过了生物等效性测试，但制剂E未通过，其AUC₀₋₂₄、AUC₀₋∞和Cmax对数转换比值的90%置信区间分别为85.2 - 100.7、85.2 - 100.7和73.8 - 100.9。