title: Why Do We Use 600 mg of Rifampicin in Tuberculosis Treatment?
abstract: 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.
authors.affiliation: University Center for Chronic Diseases Dekkerswald and Department of Pulmonary Diseases, Radboud University Nijmegen MedicalCenter, Nijmegen, The Netherlands.
authors.forename: Jakko
authors.initials: J
authors.lastname: van Ingen
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Peter R
authors.initials: PR
authors.lastname: Donald
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Diacon
authors.forename: Rodney
authors.initials: R
authors.lastname: Dawson
authors.forename: Georgette
authors.initials: G
authors.lastname: Plemper van Balen
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gillespie
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin