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. 2021 Aug 17;65(9):e0104321.
doi: 10.1128/AAC.01043-21. Epub 2021 Aug 17.

Model-Based Comparative Analysis of Rifampicin and Rifabutin Drug-Drug Interaction Profile

Vianney Tuloup  1   2 , Mathilde France  1 , Romain Garreau  1   2 , Nathalie Bleyzac  1 , Laurent Bourguignon  1   2   3 , Michel Tod  1   2   3 , Sylvain Goutelle  1   2   3
Affiliations

Model-Based Comparative Analysis of Rifampicin and Rifabutin Drug-Drug Interaction Profile

Vianney Tuloup et al. Antimicrob Agents Chemother. .

Abstract

Rifamycins are widely used for treating mycobacterial and staphylococcal infections. Drug-drug interactions (DDI) caused by rifampicin (RIF) are a major issue. We used a model-based approach to predict the magnitude of DDI with RIF and rifabutin (RBT) for 217 cytochrome P450 (CYP) substrates. On average, DDI caused by low-dose RIF were twice as potent as those caused by RBT. Contrary to RIF, RBT appears unlikely to cause severe DDI, even with sensitive CYP substrates.

Keywords: drug-drug interaction; pharmacokinetics; rifabutin; rifampicin.

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Figures

FIG 1
FIG 1
Predicted versus observed AUC ratio of substrate drugs for DDI caused by rifampicin and rifabutin reported in the literature. The solid line is the line of identity (y = x). The dotted line is y = 0.5x, and the combined dashed and dotted line is y = 2x. Abbreviations: RBT300, rifabutin at 300 mg/day (red circles); RIF600, rifampicin at 600 mg/day (cyan circles).
FIG 2
FIG 2
Box plot of predicted AUC ratios for 217 drug-drug interactions between CYP substrates and rifamycin agents. Abbreviations: RIF 600; rifampicin at 600 mg/day; RBT 300, rifabutin at 300 mg/day.
See this image and copyright information in PMC

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