title: No influence of the CYP2C19-selective inhibitor omeprazole on the pharmacokinetics of the dopamine receptor agonist rotigotine.
abstract: Rotigotine, a non-ergolinic dopamine receptor agonist administered transdermally via a patch, is metabolized by several cytochrome P-450 (CYP450) isoenzymes, including CYP2C19. This open-label, multiple-dose study evaluated the effect of omeprazole, a competitive inhibitor of CYP2C19, on the pharmacokinetics of rotigotine and its metabolites under steady-state conditions in healthy male subjects (of the extensive metabolizer phenotype, CYP2C19). Subjects received rotigotine 2 mg/24 hours on days 1-3, 4 mg/24 hours on days 4-12, and omeprazole 40 mg once daily on days 7-12 immediately after patch application. Blood and urine samples were collected on days 6 and 12 to evaluate rotigotine pharmacokinetic parameters alone and in the presence of omeprazole. Data from 37 subjects were available for pharmacokinetic analysis. Point estimates (90% confidence intervals, CI) for the ratios of AUC(0-24)SS and Cmax,SS of unconjugated rotigotine for the comparison rotigotine + omeprazole:rotigotine alone were close to 1 (0.9853 [0.9024, 1.0757] for AUC(0-24)SS and 1.0613 [0.9723, 1.1585] for Cmax,SS ) with 90% CIs within the acceptance range for bioequivalence (0.80, 1.25). Selective inhibition of CYP2C19 by omeprazole did not alter the steady-state pharmacokinetic profile of rotigotine or its metabolites. Thus, rotigotine dose adjustment is not required in patients receiving omeprazole, or other CYP2C19 inhibitors.
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Jan-Peer
authors.initials: JP
authors.lastname: Elshoff
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Jens-Otto
authors.initials: JO
authors.lastname: Andreas
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Braun
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D065689:Cytochrome P-450 CYP2C19 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013019:South Africa; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D065689:Cytochrome P-450 CYP2C19 Inhibitors; D018491:Dopamine Agonists; D054328:Proton Pump Inhibitors; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole
keywords: CYP2C19; drug-drug interactions; omeprazole; pharmacokinetics; rotigotine transdermal system