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Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity
Author(s) -
Härtter Sebastian,
Nordmark Anna,
Rose DirkMatthias,
Bertilsson Leif,
Tybring Gunnel,
Laine Kari
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01933.x
Subject(s) - caffeine , paraxanthine , cyp1a2 , melatonin , pharmacokinetics , bioavailability , pharmacology , cmax , drug , confidence interval , medicine , endocrinology , chemistry , metabolism , cytochrome p450
Aims 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 × 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 C max 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. Conclusion 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.