Agrawal S, Kaul C L, Panchagnula R
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, India.
Pharmazie. 2001 Aug;56(8):636-9.
To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.
为提高患者的依从性并降低耐药菌株出现的风险，世界卫生组织（WHO）和国际防痨和肺部疾病联盟（IUATLD）建议在直接观察短程治疗（DOTS）中使用固定剂量复方（FDC）片剂作为常规治疗方案。但使用FDC的主要问题在于制剂的质量。目前，WHO和IUATLD仅建议对FDC中的利福平与单独制剂进行生物等效性评估。为确保治疗效果，FDC的所有成分在组织部位均应具有生物利用度。此外，与其他抗结核药物相比，异烟肼的原发和获得性耐药率要高得多。因此，对一组12名健康志愿者开展了一项关于两种药物FDC中的异烟肼与单独制剂相比的相对生物利用度研究。通过正常或对数转换后的置信区间、双向方差分析和豪施克分析进行评估时，AUC0-8和AUC0-24的生物等效性限度在0.8至1.25之间。对于Cmax和Tmax，这些限度在0.7至1.43之间。因此，发现在相同剂量水平下，FDC制剂中的异烟肼与单独制剂具有生物等效性。
