Rifampicin bioavailability: a review of its pharmacology and the chemotherapeutic necessity for ensuring optimal absorption

The World Health Organization encourages the use of fixed dose combinations (FDCs) of rifampicin (RMP) and isoniazid together with pyrazinamide or pyr azinamide plus ethambutol for the treatment of tuberculosis. The main advan tages of such FDCs are the simplification of procurement and prescribing pr actices and the protection they afford against the potential selection of R MP-resistant strains of Mycobacterium tuberculosis. There is convincing evi dence, however, that the rifampicin absorption from FDCs manufactured under suboptimal conditions may be significantly impaired, and this appears to b e especially problematic with combined formulations of rifampicin, isoniazi d and pyrazinamide. In view of the marked dose-dependence of rifampicin's b acterial sterilizing action, it is therefore essential that tuberculosis co ntrol programmes only use rifampicin-containing FDCs with proven rifampicin bioavailability. The comprehensive literature on the pharmacology of rifam picin is reviewed, together with the methods employed for determining it an d its most important metabolite, desacetyl-rifampicin, in either serum or u rine. By contrast, published information concerning the absorption of rifam picin from currently marketed combined formulations and on laboratory metho ds for precisely assessing their bioavailability is very sparse. There is t herefore a crucial need to establish the quality of currently marketed rifa mpicin-containing FDCs in studies using adequate numbers of volunteers, pre cise analytical techniques and sophisticated statistical techniques.