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

Vianney Tuloup; Mathilde France; Romain Garreau; Nathalie Bleyzac; Laurent Bourguignon; Michel Tod; Sylvain Goutelle

doi:10.1128/AAC.01043-21

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

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

Authors

Vianney Tuloup^{1

2}, Mathilde France¹, Romain Garreau^{1

2}, Nathalie Bleyzac¹, Laurent Bourguignon^{1

2

3}, Michel Tod^{1

2

3}, Sylvain Goutelle^{1

2

3}

Affiliations

¹ Hospices Civils de Lyongrid.413852.9, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France.
² Université Lyon, Université Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France.
³ Université Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France.

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.

MeSH terms

Drug Interactions
Pharmaceutical Preparations*
Rifabutin / pharmacology
Rifampin / pharmacology
Rifamycins*

Substances

Pharmaceutical Preparations
Rifamycins
Rifabutin
Rifampin