Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial.
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.
Portolés
A
A
Clinical Pharmacology Studies Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain. aportoles.hcsc@salud.madrid.org
Calvo
A
A
Terleira
A
A
Laredo
L
L
Resplandy
G
G
Gorostiaga
C
C
Moreno
A
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D000077550:Ivabradine; D064747:Lansoprazole; D008297:Male; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013997:Time Factors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001552:Benzazepines; D002214:Capsules; D004791:Enzyme Inhibitors; C413689:S 18982; D013607:Tablets; D064747:Lansoprazole; D000077550:Ivabradine; D009853:Omeprazole