Volume 48, Issue 8 p. 986-994

The Effect of Oral Contraceptives on the Pharmacokinetics of Melatonin in Healthy Subjects With CYP1A2 g.-163C>A Polymorphism

Dr Johanna Hilli MD, PhD

Corresponding Author

Dr Johanna Hilli MD, PhD

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland and Clinical Pharmacology, TYKSLAB, Health Care District of Southwest Finland

Address for correspondence: Johanna Hilli, MD, PhD, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, 3rd Floor, FIN-20520 Turku, Finland; e-mail: [email protected].Search for more papers by this author
Dr Tuomas Korhonen MD

Dr Tuomas Korhonen MD

SFINX Drug Interaction Unit, Turku University Hospital, Turku, Finland

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Dr Miia Turpeinen MD, PhD

Dr Miia Turpeinen MD, PhD

Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland and Novamass Analytical Ltd, Oulu, Finland

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Mr Juho Hokkanen MSc

Mr Juho Hokkanen MSc

Department of Chemistry, University of Oulu, Oulu, Finland.

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Dr Sampo Mattila PhD

Dr Sampo Mattila PhD

Department of Chemistry, University of Oulu, Oulu, Finland.

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Dr Kari Laine MD, PhD

Dr Kari Laine MD, PhD

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland and Clinical Pharmacology, TYKSLAB, Health Care District of Southwest Finland

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First published: 07 March 2013
Citations: 30

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 Cmax 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.