Pharmacokinetics of melatonin in man: first pass hepatic metabolism.
Level 5 - mechanism / opinion, no new human data
Pharmacokinetic modeling and theoretical analysis using previously published human data
PubMed 4055987 · doi:10.1210/jcem-61-6-1214
What was done
Hepatic clearance concepts and modeling were applied to previously published data on intravenous and oral melatonin administration in humans. The authors calculated the hepatic extraction ratio, evaluated oral bioavailability, and determined endogenous melatonin production rates for healthy individuals and patients with cirrhosis.
What was found
The calculated hepatic extraction ratio was high, indicating extensive first-pass hepatic metabolism and reduced bioavailability for oral melatonin. Calculated endogenous melatonin production was 28.8 micrograms/day in healthy individuals compared to 12.3 micrograms/day in patients with cirrhosis, showing reduced daily production in addition to decreased elimination in cirrhosis.
Why it matters
This paper clarifies the physiological mechanism behind the low systemic bioavailability of oral melatonin and demonstrates that liver cirrhosis impairs endogenous melatonin synthesis alongside clearance.
Limits
The study relies on theoretical modeling of existing published data rather than new clinical measurements. The abstract provides no sample sizes, demographic characteristics, variability estimates, or statistical significance testing.
Cited by
- supports Between 70% and 90% of an oral melatonin dose is metabolized by the liver and kidney within one hour.