van Crevel R, Alisjahbana B, de Lange W C M, Borst F, Danusantoso H, van der Meer J W M, Burger D, Nelwan R H H
Department of Internal Medicine, University Medical Centre Nijmegen, The Netherlands.
Int J Tuberc Lung Dis. 2002 Jun;6(6):497-502. doi: 10.5588/09640569513002.
Although rifampicin is a key drug in tuberculosis treatment, little is known about its quality and bioavailability in countries endemic for tuberculosis. High drug levels may lead to increased toxicity, while low drug levels may predispose to treatment failure and relapse.
To investigate possible variations in the bioavailability of plasma rifampicin in tuberculosis patients in Indonesia.
Plasma concentrations of rifampicin and the rifampicin content of drug formulations in use were measured among 62 non-selected tuberculosis patients in Jakarta, Indonesia.
Plasma concentrations of rifampin were generally low: 70% of patients had 2-hour plasma concentrations (Cmax) below 4 mg/L. No toxic plasma concentrations of rifampicin (>20 mg/L) were found. The strongest predictive factor for the magnitude of rifampicin concentrations was the drug manufacturer. The rifampicin content of the different drug preparations used was normal (90.5-103.6% of the reference standard). No association was found between low plasma rifampicin concentrations and delayed sputum conversion or treatment failure.
The unexpectedly low plasma concentrations of rifampicin in this setting are most likely due to reduced bioavailability of local drug preparations, as the rifampicin content of the drug preparations was found to be normal. The clinical significance of these findings remains to be determined.
尽管利福平是结核病治疗的关键药物，但在结核病流行国家，对其质量和生物利用度了解甚少。药物水平过高可能导致毒性增加，而药物水平过低可能易引发治疗失败和复发。
调查印度尼西亚结核病患者血浆中利福平生物利用度的可能差异。
在印度尼西亚雅加达的62例未经挑选的结核病患者中，测量了利福平的血浆浓度以及所用药物制剂中的利福平含量。
利福平的血浆浓度普遍较低：70%的患者2小时血浆浓度（Cmax）低于4mg/L。未发现利福平的毒性血浆浓度（>20mg/L）。利福平浓度大小的最强预测因素是药品制造商。所用不同药物制剂中的利福平含量正常（为参考标准的90.5-103.6%）。血浆利福平浓度低与痰菌转阴延迟或治疗失败之间未发现关联。
在这种情况下，利福平血浆浓度意外偏低很可能是由于当地药物制剂的生物利用度降低，因为发现药物制剂中的利福平含量正常。这些发现的临床意义尚待确定。
