ArticleClinical drug investigation2012
Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects.
Article in Clinical drug investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 26 citations in OpenAlex.
- Reassessing Ivabradine: Potential Benefits and Risks in Atrial Fibrillation Therapy.Cardiovascular drugs and therapy · 2025Review
- Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug-Drug Interactions of Phenytoin.Pharmaceutics · 2023Article
- Alternatives to rifampicin: A review and perspectives on the choice of strong CYP3A inducers for clinical drug-drug interaction studies.Clinical and translational science · 2022Review
- The Effect of Ivabradine on the Human Atrial Myocardial Contractility in anCardiology research and practice · 2019Article
- Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.Neurochemical research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhenytoin is an inductor of the main metabolizing enzyme of ivabradine and it could influence its pharmacokinetics. Changes in ivabradine pharmacokinetics could have clinical significance regarding the safety of the treatment.
objectiveThe study objective was evaluation of the pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects.
methodsA single dose of ivabradine 10 mg was administered alone or in combination with phenytoin 150 mg to 18 healthy subjects in a two-treatment study design, separated by 5 days in which the phenytoin alone was administered at a dose of 150 mg twice daily. Plasma concentrations of ivabradine were determined during a 12-hour period following drug administration, using a high-throughput liquid chromatography coupled with mass spectrometry analytical method. Pharmacokinetic parameters of ivabradine administered in each treatment were calculated using non-compartmental analysis and compared to determine if the differences were statistically significant.
resultsIn the two treatment periods, the mean ± SD peak plasma concentrations (C(max)) were 18.6 ± 8.0 ng/mL (ivabradine alone) and 6.5 ± 3.1 ng/mL (ivabradine after pre-treatment with phenytoin). The mean ± SD times taken to reach C(max) (t(max)) were 1.2 ± 0.7 h and 0.8 ± 0.6 h, respectively, and the total areas under the plasma concentration-time curve from time zero to infinity (AUC(∞)) were 62.3 ± 18.7 ng · h/mL and 19.2 ± 17.0 ng · h/mL, respectively. Statistically significant differences were observed for the C(max) and AUC(∞) of ivabradine when administered alone or with phenytoin, whereas for t(max) and the half-life the differences were non-significant.
conclusionThis study showed that phenytoin has an important effect on the pharmacokinetics of ivabradine in healthy subjects, reducing its bioavailability by approximately 70%.
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