Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity

Abstract

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 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.

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.

Figures

Figure 1

Melatonin serum concentration after oral administration of melatonin alone (closed circles, dotted line) or together with caffeine (3 × 200 mg) given 1 h before and 1 and 3 h after melatonin intake (open squares, solid line). Melatonin serum concentrations were significantly (*P < 0.05; **P < 0.01) higher at all time points between 0.5 and 6 h after melatonin intake when caffeine was coadministered