Rifampicin bioavailability: a review of its pharmacology and the chemotherapeutic necessity for ensuring optimal absorption
Abstract:The World Health Organization encourages the use of fixed dose combinations (FDCs) of rifampicin (RMP) and isoniazid together with pyrazinamide or pyrazinamide plus ethambutol for the treatment of tuberculosis. The main advantages of such FDCs are the simplification of procurement and prescribing practices and the protection they afford against the potential selection of RMP-resistant strains of Mycobacterium tuberculosis. There is convincing evidence, however, that the rifampicin absorption from FDCs manufactured under suboptimal conditions may be significantly impaired, and this appears to be especially problematic with combined formulations of rifampicin, isoniazid and pyrazinamide. In view of the marked dose-dependence of rifampicin's bacterial sterilizing action, it is therefore essential that tuberculosis control programmes only use rifampicin-containing FDCs with proven rifampicin bioavailability. The comprehensive literature on the pharmacology of rifampicin is reviewed, together with the methods employed for determining it and its most important metabolite, desacetyl-rifampicin, in either serum or urine. By contrast, published information concerning the absorption of rifampicin from currently marketed combined formulations and on laboratory methods for precisely assessing their bioavailability is very sparse. There is therefore a crucial need to establish the quality of currently marketed rifampicin-containing FDCs in studies using adequate numbers of volunteers, precise analytical techniques and sophisticated statistical techniques.
Document Type: Review Article
Publication date: November 1, 1999
The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.
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