Orally given melatonin may serve as a probe drug for cytochrome P450 1A2 activity in vivo: a pilot study.
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.


CONCLUSIONS
Melatonin might be developed as an alternative to caffeine as a probe drug for CYP1A2 phenotyping.
Härtter
S
S
Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Ursing
C
C
Morita
S
S
Tybring
G
G
von Bahr
C
C
Christensen
M
M
Röjdmark
S
S
Bertilsson
L
L
D000284:Administration, Oral; D000328:Adult; D002110:Caffeine / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010641:Phenotype; D010865:Pilot Projects; D012016:Reference Values; D013997:Time Factors
D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D008550:Melatonin; C012365:6-hydroxymelatonin