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

Vianney Tuloup1,2, Mathilde France1, Romain Garreau1,2

  • 1Hospices Civils de Lyongrid.413852.9, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France.

Antimicrobial Agents and Chemotherapy
|July 6, 2021
PubMed

Insights

Rifampicin (RIF) and rifabutin (RBT) treat infections, but RIF causes significant drug-drug interactions (DDI). Our study found RIF

Area of Science:

  • Pharmacology and Drug Metabolism
  • Infectious Diseases
  • Drug Interactions

Background:

  • Rifamycins, including rifampicin (RIF) and rifabutin (RBT), are crucial for treating mycobacterial and staphylococcal infections.
  • Drug-drug interactions (DDIs) involving RIF are a significant clinical concern due to its potent induction of cytochrome P450 (CYP) enzymes.
  • Understanding the comparative DDI potential of RIF and RBT is essential for optimizing patient safety and treatment efficacy.

Purpose of the Study:

  • To predict and compare the magnitude of drug-drug interactions (DDIs) caused by rifampicin (RIF) and rifabutin (RBT) across a wide range of cytochrome P450 (CYP) substrates.
  • To assess the potential for severe DDIs with RIF and RBT, particularly in relation to sensitive CYP substrates.

Main Methods:

  • A model-based approach was employed to simulate and quantify the DDI potential of RIF and RBT.
  • The study analyzed 217 known cytochrome P450 (CYP) substrates to predict the impact of RIF and RBT on their metabolism.
  • Quantitative predictions were made regarding the magnitude of interaction for each drug-substrate pair.

Main Results:

  • On average, low-dose RIF was predicted to cause DDIs twice as potent as those caused by RBT.
  • RBT demonstrated a significantly lower potential for causing DDIs compared to RIF across the evaluated CYP substrates.
  • RBT is unlikely to cause severe DDIs, even when co-administered with highly sensitive CYP substrates, unlike RIF.

Conclusions:

  • Rifampicin (RIF) poses a greater risk for significant drug-drug interactions compared to rifabutin (RBT).
  • Rifabutin (RBT) presents a safer alternative in terms of DDI potential, especially for patients on medications metabolized by sensitive cytochrome P450 enzymes.
  • Model-based predictions highlight the importance of considering DDI profiles when selecting between RIF and RBT for treating infections.
Keywords:
drug-drug interactionpharmacokineticsrifabutinrifampicin

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