Pharmacokinetics of melatonin in man: first pass hepatic metabolism.

Hepatic clearance concepts were applied to existing data on iv and oral administration of melatonin to man. A high hepatic extraction ratio was calculated, suggesting prominent first pass hepatic metabolism and reduced bioavailability for orally administered melatonin. Using clearance parameters and previous data, endogenous production rates for melatonin were determined for normal individuals and patients with cirrhosis. Normal melatonin production was 28.8 micrograms/day, while the production rate for cirrhotic patients was 12.3 micrograms/day. Thus, not only do cirrhotic patients have decreased melatonin elimination, as noted in the original report, but they also have decreased daily melatonin production.