The 600-mg once daily dose of rifampicin plays a key role in tuberculosis treatment. The evidence underpinning this dose is scant. A review of the historical literature identified 3 strands of reasoning. The first is the pharmacokinetic argument: The 600-mg dose yields serum drug concentrations well above the minimum inhibitory concentration of rifampicin against Mycobacterium tuberculosis. The second is the argument that adverse events may be dose related. The third is the economic argument: Rifampicin was prohibitively expensive at the time of its introduction. Recent in vitro, animal, and early bactericidal activity studies suggest that the 600-mg once daily dose is at the lower end of the dose-response curve, refuting the pharmacokinetic argument. The reduced cost and the lack of evidence of toxicity at higher daily doses remove the other arguments. To optimize tuberculosis treatment, the clinical value of higher doses of rifampicin should be tested in clinical trials.
