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Orally given melatonin may serve as a probe drug for cytochrome P450 1A2 activity in vivo: a pilot study
S Härtter1, C Ursing, S Morita
1Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Background:
Melatonin is a hormone that is metabolized by cytochrome P450 (CYP) 1A2 to its main primary metabolite 6-hydroxymelatonin. We therefore evaluated the utility of oral melatonin as a marker of hepatic CYP1A2 activity.
Methods:
Twenty-five milligrams of melatonin was given at 9:30 am to 12 healthy Swedish volunteers, who had previously been phenotyped for CYP1A2 with caffeine. Melatonin and conjugated 6-hydroxymelatonin were analyzed by liquid chromatography-mass spectrometry in blood samples taken between 0.5 and 6.5 hours after drug intake. Serum concentrations of melatonin and conjugated 6-hydroxymelatonin, or their ratio at different time points, and the apparent melatonin clearance were tested for correlation with caffeine clearance.
Results:
We found a significant correlation between apparent clearance of melatonin and caffeine clearance with a Spearman rank correlation coefficient (Rs) of 0.75 (P =.005). The melatonin concentration 1.5 hours after administration also closely correlated with the caffeine clearance (Rs = -0.62; P =.03). Inclusion of conjugated 6-hydroxymelatonin gave no closer correlations.
Conclusion:
Melatonin might be developed as an alternative to caffeine as a probe drug for CYP1A2 phenotyping.