Ralf Stemkens, Veronique de Jager, Rodney Dawson, Andreas H Diacon, Kim Narunsky, Sherman D Padayachee, Martin J Boeree, Stijn W van Beek, Angela Colbers, Marieke J H Coenen, Elin M Svensson, Uwe Fuhr, Patrick P J Phillips, Lindsey H M Te Brake, Rob E Aarnoutse
Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30)...
September 28, 2023: Antimicrobial Agents and Chemotherapy