ArticleBritish journal of clinical pharmacology2021
Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects.
Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Population pharmacokinetics of selexipag for dose selection and confirmation in pediatric patients with pulmonary arterial hypertension.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- Oral P2YEuropean cardiology · 2025Review
- CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.Drug design, development and therapy · 2025Review
- Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2022Review
- Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles.Pharmaceutical biology · 2022Article
- Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.Chest · 2022Review
- Article
- Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects.British journal of clinical pharmacology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsSelexipag is a prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension. Cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. This study evaluated the interaction of selexipag and clopidogrel, a CYP2C8 inhibitor.
methodsThe study had a 2-treatment, 1-sequence, crossover design. Pharmacokinetics (PK) and CYP2C8 genotype were assessed in healthy male subjects administered selexipag (200 μg twice daily [b.i.d.]) alone or with clopidogrel (300 mg single dose or 75 mg once daily [o.d.]). PK modelling and simulation were conducted to support dosing recommendations.
resultsClopidogrel had a comparatively small effect on selexipag (<1.5-fold difference in any PK variable). For ACT-333679, the major contributor to the drug effect, the area under the plasma concentration-time curve during a dose interval and the maximum plasma concentration increased 2.25-fold (90% confidence interval [CI] 2.06, 2.46) and 1.69-fold (90% CI 1.55, 1.84), respectively with clopidogrel 300 mg and 2.70-fold (90% CI 2.45, 2.96) and 1.90-fold (90% CI 1.72, 2.11), respectively with clopidogrel 75 mg. The effect of clopidogrel on selexipag and ACT-333679 exposure was comparable for all identified CYP2C8 genotypes. PK simulations predicted comparable exposure to ACT-333679 following selexipag 400 μg b.i.d., 400 μg o.d. in combination with clopidogrel 75 mg o.d and 200 μg b.i.d. with clopidogrel 75 mg o.d.
conclusionResults suggest that ACT-333679 exposure can be maintained within the therapeutic range by reducing selexipag dosing frequency to o.d. or dose to half, when selexipag is coadministered with clopidogrel.
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