Trial reportClinical pharmacokinetics2013
Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects.
Trial report in Clinical pharmacokinetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Endothelin receptor antagonists for pulmonary arterial hypertension.The Cochrane database of systematic reviews · 2021Pooled it
- Investigation of mutual pharmacokinetic interactions between macitentan, a novel endothelin receptor antagonist, and sildenafil in healthy subjects.British journal of clinical pharmacology · 2014Trial
- Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects.Clinical drug investigation · 2014Trial
- Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo.Drug design, development and therapy · 2025Article
- Liver injury associated with endothelin receptor antagonists: a pharmacovigilance study based on FDA adverse event reporting system data.International journal of clinical pharmacy · 2024Article
- Effects of bergapten on the pharmacokinetics of macitentan in rats bothFrontiers in pharmacology · 2023Article
- Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.Chest · 2022Review
- A Population Pharmacokinetic Model of Macitentan and Its Active Metabolite Aprocitentan in Healthy Volunteers and Patients with Pulmonary Arterial Hypertension.Clinical pharmacokinetics · 2021Article
- Analysis of Clinical Drug-Drug Interaction Data To Predict Magnitudes of Uncharacterized Interactions between Antiretroviral Drugs and Comedications.Antimicrobial agents and chemotherapy · 2018Article
- Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?Vascular health and risk management · 2018Review
- Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug-Drug Interactions.Clinical pharmacokinetics · 2016Article
- Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension.Drug design, development and therapy · 2016Review
- Possible drug-drug interaction in dogs and cats resulted from alteration in drug metabolism: A mini review.Journal of advanced research · 2015Review
- Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan.Clinical pharmacokinetics · 2015Review
- Review
- Macitentan for the treatment of pulmonary arterial hypertension.Vascular health and risk management · 2014Review
- Macitentan: first global approval.Drugs · 2014Article
- New horizons in pulmonary arterial hypertension therapies.European respiratory review : an official journal of the European Respiratory Society · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMacitentan is a potent, orally active, non-peptide antagonist of endothelin receptors with tissue-targeting properties, currently undergoing clinical development for the treatment of pulmonary arterial hypertension. The formation of its active metabolite, ACT-132577, as well as overall elimination of the drug, is catalyzed by the cytochrome P450 (CYP) system, predominantly CYP3A4 and to a lesser extent CYP2C19 isoenzyme. Macitentan is not a substrate of P-glycoprotein. Hepatic uptake is mostly driven by passive diffusion and is not dependent on organic anion-transporting polypeptide transport. This study aimed to investigate the magnitude of a possible effect of a potent CYP3A4 inhibitor, ketoconazole, on the pharmacokinetics of macitentan.
methodsIn a two-period, randomized, open-label, crossover study, 10 healthy subjects received each of the following treatments: Treatment A in which a single oral dose of 10 mg macitentan was administered on day 1 and Treatment B which consisted of initial daily treatment with ketoconazole 400 mg for 4 days, coadministration of macitentan and ketoconazole on the fifth day and continued administration of ketoconazole for 19 additional days.
resultsIn the presence of ketoconazole, the exposure to macitentan expressed as area under the plasma concentration-time curve was increased by approximately a factor of 2 and to ACT-132577 was reduced by approximately 26 %. Macitentan was well-tolerated with or without ketoconazole in this study and no relevant differences in safety parameters between the treatments were observed.
conclusionsAlthough macitentan metabolism is indeed affected by CYP3A4 inhibition, the changes are not considered to be clinically significant and macitentan can be administered concomitantly with CYP3A4 inhibitors without need for dose adjustment.
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