The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism

J Clin Pharmacol. 2008 Aug;48(8):986-94. doi: 10.1177/0091270008318669. Epub 2008 May 19.


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.

MeSH terms

  • Adult
  • Alleles
  • Area Under Curve
  • Attention / drug effects
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Cytochrome P-450 CYP1A2 / genetics*
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP1A2 Inhibitors*
  • Drug Interactions
  • Female
  • Genotype
  • Half-Life
  • Humans
  • Hydroxylation
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacokinetics*
  • Polymorphism, Genetic / genetics*


  • Contraceptives, Oral, Hormonal
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP1A2
  • Melatonin