Does hepatic metabolism of melatonin affect the endogenous serum melatonin level in man?

Melatonin (MT) is metabolized in the liver by cytochrome P450 (CYP) 1A2 but its importance for the metabolic process has not been fully elucidated. Therefore, the objective of this investigation was to study whether patients with different CYP1A2 activity would have different nocturnal serum MT levels. For that purpose serum MT concentrations were determined every second hour during the night in 12 healthy subjects and their MT areas under the curve (MT-AUCs) were calculated. Caffeine (CA) clearance was determined in advance. It is generally accepted that CA clearance reflects CYP1A2 activity. This made it possible to evaluate whether a relationship prevails between endogenous MT-AUCs and CYP1A2 activity. If CYP1A2 is of importance for the metabolism of MT one would expect to find an inverse correlation between the MT-AUCs and the CA clearance. However, such correlation did not exist in the current study (Rs=-0.021, NS). Since endogenous MT-AUC is dependent not only on MT elimination by CYP1A2 but also on MT secretion, it is possible that an increased MT secretion counter-balances an increased hepatic MT metabolism. If so, this could explain why the MT-AUCs and the CA clearance values were not inversely correlated in this study.