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The Effect of Oral Contraceptives on the Pharmacokinetics of Melatonin in Healthy Subjects With CYP1A2 g.‐163C>A Polymorphism
Author(s) -
Hilli Johanna,
Korhonen Tuomas,
Turpeinen Miia,
Hokkanen Juho,
Mattila Sampo,
Laine Kari
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008318669
Subject(s) - melatonin , cyp1a2 , pharmacokinetics , endocrinology , medicine , genotype , chemistry , metabolism , cytochrome p450 , biochemistry , gene
The effect of oral contraceptives (OCs) on melatonin metabolism was studied in 29 subjects genotyped for CYP1A 2 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.