Trial reportClinical drug investigation2014
Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects.
Trial report in Clinical drug investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 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
- Prolonged Prothrombin Time due to Drug-Drug Interaction of Warfarin after the Change from Bosentan to Macitentan: A Case of Pharmacist Intervention in the Outpatient Clinic.The Kobe journal of medical sciences · 2025Article
- Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects.Drugs in R&D · 2024Article
- Aprocitentan: A new development of resistant hypertension.Journal of clinical hypertension (Greenwich, Conn.) · 2023Review
- Effects of bergapten on the pharmacokinetics of macitentan in rats bothFrontiers in pharmacology · 2023Article
- Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided.British journal of clinical pharmacology · 2018Article
- Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?Vascular health and risk management · 2018Review
- [Pulmonary hypertension : What is new in therapy?].Der Anaesthesist · 2016Article
- 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
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMacitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of pulmonary arterial hypertension (PAH). Warfarin, an anticoagulant often prescribed to patients with PAH, has a narrow therapeutic index and is prone to potential interactions with drugs. This study assessed the effects of macitentan on the pharmacokinetics and pharmacodynamics of single-dose warfarin in healthy subjects.
methodsThis was a randomised, open-label, single-centre, two-way crossover (treatment A followed by treatment B, or vice versa), phase I study in 14 healthy male subjects. Treatment A was a loading dose of macitentan 30 mg on Day 1 followed by 10 mg once daily for 8 days, with a single 25 mg dose of warfarin on Day 4. Treatment B was a single dose of warfarin on Day 1. Blood samples were assessed for warfarin pharmacokinetics (R- and S-warfarin) and pharmacodynamics [international normalised ratio (INR) and factor VII]. Plasma trough concentrations of macitentan and its active metabolite (ACT-132577) and the safety and tolerability of each treatment were also assessed.
resultsPlasma concentrations of R- and S-warfarin were similar in both treatment periods. Warfarin did not affect the mean trough plasma concentrations of macitentan or ACT-132577. Macitentan did not affect the pharmacodynamics of warfarin; the mean INR and factor VII activity versus time profiles were similar with and without macitentan.
conclusionsThe absence of effect of macitentan on the pharmacokinetics and pharmacodynamics of a single dose of warfarin suggests that both drugs can be concomitantly administered without need for dose adjustment.
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