Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity.
OBJECTIVE
The aim of this study was to assess the influence of concomitant caffeine intake on the pharmacokinetics of oral melatonin, a probe drug for CYP1A2 activity.


METHODS
Twelve healthy subjects, six smokers and six nonsmokers, were given melatonin (6 mg) either alone or in combination with caffeine (3 x 200 mg). Blood samples for the analysis of melatonin or caffeine and paraxanthine were taken from 1 h before until 6 h after intake of melatonin. Subjects were genotyped with respect to the CYP1A2*1F (C734A) polymorphism.


RESULTS
When caffeine was coadministered the Cmax and AUC of melatonin were increased on average by 142% (P = 0.001, confidence interval on the difference 44, 80%) and 120% (P < 0.001, confidence interval on the difference 63, 178%), respectively. The inhibitory effect of caffeine was more pronounced in nonsmokers and in individuals with the *1F/*1F genotype.


CONCLUSIONS
The results of this study revealed a pronounced effect of caffeine on the bioavailability of orally given melatonin, most probably due to inhibition of CYP1A2 activity.
Härtter
Sebastian
S
Department of Psychiatry and Institute of Occupational, Social and Environmental Medicine University of Mainz, Mainz, Germany. sepp@psychiatrie.klinik.uni-mainz.de
Nordmark
Anna
A
Rose
Dirk-Matthias
DM
Bertilsson
Leif
L
Tybring
Gunnel
G
Laine
Kari
K
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000494:pharmacology*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004338:Drug Combinations; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D008550:Melatonin