McIlleron H, Wash P, Burger A, Folb P, Smith P
Division of Pharmacology, University of Cape Town Medical School, South Africa.
Int J Tuberc Lung Dis. 2002 Apr;6(4):356-61.
A pharmacokinetic study of rifampicin, isoniazid, pyrazinamide and ethambutol in 118 tuberculosis patients revealed low and variable concentrations of rifampicin after 2 months of treatment on standard daily doses. A group of 53 patients exposed to specific batches of formulations containing rifampicin alone showed particularly low and variable levels of the drug. The national drug regulatory authority subsequently withdrew the batches in question, as sufficient bioavailability data had not been submitted after what the manufacturer had considered to be a minor formulation change. The evidence supports initiatives to implement bioavailability testing of new formulations (and of established formulations subsequent to changes in the manufacturing process) prior to distribution. Concerns about the bioavailability of rifampicin-containing products, including those with adequate dissolution profiles, should not be confined to fixed-dose combination anti-tuberculosis drugs, but should also be applied to single drug formulations.
一项针对118名结核病患者的利福平、异烟肼、吡嗪酰胺和乙胺丁醇的药代动力学研究显示，在接受标准日剂量治疗2个月后，利福平的浓度较低且变化不定。一组53名仅接触含利福平特定批次制剂的患者，该药物的水平尤其低且变化不定。国家药品监管机构随后撤回了相关批次，因为在制造商认为是微小剂型变更后，未提交足够的生物利用度数据。有证据支持在新制剂（以及生产工艺变更后的现有制剂）分发前开展生物利用度测试的举措。对含利福平产品生物利用度的担忧，包括那些具有充分溶出度曲线的产品，不应仅限于固定剂量复方抗结核药物，还应适用于单一药物制剂。
