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First published on May 19, 2008, doi:10.1177/0091270008318669

The Journal of Clinical Pharmacology 2008;48:986.

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©© 2008 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270008318669

Article

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

Johanna Hilli 1*, Tuomas Korhonen 2, Miia Turpeinen 3, Juho Hokkanen 4, Sampo Mattila 4, and Kari Laine 1

1 Department of Pharmacology, Drug Development and Therapeutics, University of Turku
2 SFINX Drug Interaction Unit, Turku University Hospital
3 Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland and Novamass Analytical Ltd, Oulu, Finland
4 Department of Chemistry, University of Oulu, Oulu, Finland

* To whom correspondence should be addressed. E-mail: johanna.hilli{at}utu.fi.


  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.
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