ArticleBritish journal of clinical pharmacology2008
Maraviroc: in vitro assessment of drug-drug interaction potential.
Article in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects.Journal of clinical pharmacology · 2019Trial
- Impact of low-dose ritonavir on danoprevir pharmacokinetics: results of computer-based simulations and a clinical drug-drug interaction study.Clinical pharmacokinetics · 2012Trial
- Pharmacokinetic effects of coadministration of lersivirine with raltegravir or maraviroc in healthy subjects.Antimicrobial agents and chemotherapy · 2012Trial
- Interactions between alcohol and the HIV entry inhibitor Maraviroc.Journal of the International Association of Providers of AIDS CareTrial
- Improving In Vitro-In Vivo Correlation (IVIVC) for Lipid-Based Formulations: Overcoming Challenges and Exploring Opportunities.Pharmaceutics · 2025Review
- Application of Physiologically Based Pharmacokinetic Modeling in the Research of Anti-HIV Drugs.Current drug metabolism · 2025Review
- Past HIV-1 Medications and the Current Status of Combined Antiretroviral Therapy Options for HIV-1 Patients.Pharmaceutics · 2021Review
- Physiologically Based Pharmacokinetic Model Qualification and Reporting Procedures for Regulatory Submissions: A Consortium Perspective.Clinical pharmacology and therapeutics · 2018Review
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions with Efavirenz Involving Simultaneous Inducing and Inhibitory Effects on Cytochromes.Clinical pharmacokinetics · 2017Article
- Concomitant nevirapine impacts pharmacokinetic exposure to the antimalarial artemether-lumefantrine in African children.PloS one · 2017Article
- Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics.Neurotoxicity research · 2016Review
- Towards a Best Practice Approach in PBPK Modeling: Case Example of Developing a Unified Efavirenz Model Accounting for Induction of CYPs 3A4 and 2B6.CPT: pharmacometrics & systems pharmacology · 2016Article
- Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV.Clinical pharmacokinetics · 2015Article
- Maraviroc: a review of its use in HIV infection and beyond.Drug design, development and therapy · 2015Review
- Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.Clinical pharmacokinetics · 2015Review
- Use of in vitro to in vivo extrapolation to predict the optimal strategy for patients switching from efavirenz to maraviroc or nevirapine.Clinical pharmacokinetics · 2015Article
- Pharmacokinetic and pharmacodynamic drug interactions with ethanol (alcohol).Clinical pharmacokinetics · 2014Review
- CYP3A5 genotype impacts maraviroc concentrations in healthy volunteers.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Clinically relevant drug-drug interactions between antiretrovirals and antifungals.Expert opinion on drug metabolism & toxicology · 2014Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo characterize the cytochrome P450 enzyme(s) responsible for the N-dealkylation of maraviroc in vitro, and predict the extent of clinical drug-drug interactions (DDIs).
methodsHuman liver and recombinant CYP microsomes were used to identify the CYP enzyme responsible for maraviroc N-dealkylation. Studies comprised enzyme kinetics and evaluation of the effects of specific CYP inhibitors. In vitro data were then used as inputs for simulation of DDIs with ketoconazole, ritonavir, saquinavir and atazanvir, using the Simcyptrade mark population-based absorption, distribution, metabolism and elimination (ADME) simulator. Study designs for simulations mirrored those actually used in the clinic.
resultsMaraviroc was metabolized to its N-dealkylated product via a single CYP enzyme characterized by a K(m) of 21 microM and V(max) of 0.45 pmol pmol(-1) min(-1) in human liver microsomes and was inhibited by ketoconazole (CYP3A4 inhibitor). In a panel of recombinant CYP enzymes, CYP3A4 was identified as the major CYP responsible for maraviroc metabolism. Using recombinant CYP3A4, N-dealkylation was characterized by a K(m) of 13 microM and a V(max) of 3 pmol pmol(-1) CYP min(-1). Simulations therefore focused on the effect of CYP3A4 inhibitors on maraviroc pharmacokinetics. The simulated median AUC ratios were in good agreement with observed clinical changes (within twofold in all cases), although, in general, there was a trend for overprediction in the magnitude of the DDI.
conclusionMaraviroc is a substrate for CYP3A4, and exposure will therefore be modulated by CYP3A4 inhibitors. Simcyptrade mark has successfully simulated the extent of clinical interactions with CYP3A4 inhibitors, further validating this software as a good predictor of CYP-based DDIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.