title: The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism.
abstract: The effect of oral contraceptives (OCs) on melatonin metabolism was studied in 29 subjects genotyped for CYP1A2 SNP g.-163C>A polymorphism. Plasma melatonin and 6-OH-melatonin concentrations were measured after a 6-mg dose of melatonin using a validated liquid chromatography/mass spectrometry method. The mean melatonin AUC and C(max) values were 4- to 5-fold higher in OC users than in non-OC users (P < .0001), whereas the weight-adjusted clearance was significantly lower in OC users (P < .0001). No significant difference in melatonin pharmacokinetics between the genotypes and no additional effect by the genotype on the OC-induced increase in melatonin exposure were evident. Melatonin exposure had no significant effect on the subjects' state of alertness. In conclusion, a significant inhibitory effect of OCs on the CYP1A2-catalyzed melatonin metabolism was seen; thereby, OC use can alter CYP1A2-phenotyping results.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, 3rd Floor, FIN-20520 Turku, Finland. johanna.hilli@utu.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Hilli
authors.forename: Tuomas
authors.initials: T
authors.lastname: Korhonen
authors.forename: Miia
authors.initials: M
authors.lastname: Turpeinen
authors.forename: Juho
authors.initials: J
authors.lastname: Hokkanen
authors.forename: Sampo
authors.initials: S
authors.lastname: Mattila
authors.forename: Kari
authors.initials: K
authors.lastname: Laine
mesh_terms: D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D001288:Attention / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D003278:Contraceptives, Oral, Hormonal; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019388:Cytochrome P-450 CYP1A2; D008550:Melatonin