Higher doses of rifampicin as a means of more efficient use of this pivotal TB drug has shown
promising results and might become standard in future. This means that higher doses of
rifampicin will be co-administered with many other drugs taken by TB patients, including
anti-retroviral, anti-diabetic, cardiovascular and other drugs. Therefore, in this study the
aim is to quantitatively assess the drug interaction potential of high dose rifampicin (~40
mg/kg daily dose, the currently available maximum tolerated dose) with respect to five major
human drug-metabolizing CYP enzymes and P-gp in comparison to the conventional dose of 10
mg/kg daily in pulmonary TB patients. A phenotyping approach with single administration of
several selective substrates for multiple enzymes will be used, in order to prevent multiple
drug-drug interaction studies.