ArticleClinical pharmacokinetics2016
Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug-Drug Interactions.
Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach.Frontiers in pharmacology · 2025Article
- Development and application of a PBPK modeling strategy to support antimalarial drug development.CPT: pharmacometrics & systems pharmacology · 2023Article
- Predicting the Drug-Drug Interaction Mediated by CYP3A4 Inhibition: Method Development and Performance Evaluation.The AAPS journal · 2021Article
- A Population Pharmacokinetic Model of Macitentan and Its Active Metabolite Aprocitentan in Healthy Volunteers and Patients with Pulmonary Arterial Hypertension.Clinical pharmacokinetics · 2021Article
- Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications.Cardiovascular drugs and therapy · 2021Review
- Comprehensive PBPK model to predict drug interaction potential of Zanubrutinib as a victim or perpetrator.CPT: pharmacometrics & systems pharmacology · 2021Article
- Completion and Adverse Drug Events of Latent Tuberculosis Infection Treatment in Patients Receiving Dialysis: Predictors and Impacts of Different Regimens in a Prospective Cohort Study.Antimicrobial agents and chemotherapy · 2021Article
- The endothelin receptor antagonist macitentan for the treatment of pulmonary arterial hypertension: A cross-species comparison of its cytochrome P450 induction pattern.Pharmacology research & perspectives · 2020Article
- Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?Vascular health and risk management · 2018Review
- Management of Blood Loss in Hip Arthroplasty: Korean Hip Society Current Consensus.Hip & pelvis · 2017Review
- Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan.Clinical pharmacokinetics · 2015Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMacitentan is a novel dual endothelin receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). It is metabolized by cytochrome P450 (CYP) enzymes, mainly CYP3A4, to its active metabolite ACT-132577.
methodsA physiological-based pharmacokinetic (PBPK) model was developed by combining observations from clinical studies and physicochemical parameters as well as absorption, distribution, metabolism and excretion parameters determined in vitro.
resultsThe model predicted the observed pharmacokinetics of macitentan and its active metabolite ACT-132577 after single and multiple dosing. It performed well in recovering the observed effect of the CYP3A4 inhibitors ketoconazole and cyclosporine, and the CYP3A4 inducer rifampicin, as well as in predicting interactions with S-warfarin and sildenafil. The model was robust enough to allow prospective predictions of macitentan-drug combinations not studied, including an alternative dosing regimen of ketoconazole and nine other CYP3A4-interacting drugs. Among these were the HIV drugs ritonavir and saquinavir, which were included because HIV infection is a known risk factor for the development of PAH.
conclusionThis example of the application of PBPK modeling to predict drug-drug interactions was used to support the labeling of macitentan (Opsumit).
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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 Socratic graph.