Abstract
The effects of omeprazole and lansoprazole (CYP3A4 inhibitors) on the pharmacokinetics of a single dose of ivabradine (metabolized via CYP3A4) and its active metabolite (S18982) were assessed. Pharmacodynamics and safety were secondary objectives. An open-label, randomized, crossover, phase I, pharmacokinetic interaction design was used. Volunteers received a single oral dose of ivabradine (10 mg), were randomized to receive either omeprazole (40 mg) or lansoprazole (60 mg) for 5 days, and were administered an ivabradine dose on the sixth day. Crossover was performed after washout. Pharmacokinetic parameters for ivabradine did not vary significantly after omeprazole (C(max): 45.0 +/- 36.6 vs 42.7 +/- 27.6 ng/mL, P = .98; AUC: 128 +/- 87 vs 126 +/- 63 ng/mL, P = .82) or lansoprazole administration (C(max): 45.0 +/- 36.6 vs 41.3 +/- 29.4 ng/mL, P = .70; AUC: 128 +/- 87 vs 123 +/- 50, P = .73). Analyses of S18982 pharmacokinetic parameters showed similar results. Coadministration of either omeprazole or lansoprazole did not significantly affect the pharmacokinetics of a single dose of ivabradine. No pharmacodynamic interaction or safety concerns were evidenced.
Publication types
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Clinical Trial, Phase I
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
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2-Pyridinylmethylsulfinylbenzimidazoles / adverse effects
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2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics*
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Administration, Oral
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Adolescent
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Adult
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Anti-Ulcer Agents / administration & dosage
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Anti-Ulcer Agents / adverse effects
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Anti-Ulcer Agents / pharmacokinetics
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Area Under Curve
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Benzazepines / administration & dosage
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Benzazepines / adverse effects
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Benzazepines / pharmacokinetics*
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Capsules
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Chromatography, High Pressure Liquid
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Cross-Over Studies
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Drug Interactions
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Electrocardiography
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / adverse effects
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Enzyme Inhibitors / pharmacokinetics
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Female
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Half-Life
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Heart Rate / drug effects
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Humans
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Hypotension, Orthostatic / chemically induced
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Ivabradine
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Lansoprazole
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Male
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Metabolic Clearance Rate
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Omeprazole / administration & dosage
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Omeprazole / adverse effects
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Omeprazole / pharmacokinetics*
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Tablets
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Time Factors
Substances
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2-Pyridinylmethylsulfinylbenzimidazoles
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Anti-Ulcer Agents
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Benzazepines
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Capsules
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Enzyme Inhibitors
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S 18982
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Tablets
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Lansoprazole
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Ivabradine
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Omeprazole