The absolute bioavailability of oral melatonin.
Level 2 - randomized trial
Randomized crossover pharmacokinetic trial in healthy humans
PubMed 10883420 · doi:10.1177/00912700022009422
What was done
Twelve normal healthy volunteers received 2 mg intravenous melatonin, 2 mg oral melatonin, and 4 mg oral melatonin in a randomized crossover design. Blood was sampled over approximately eight estimated half-lives to determine absolute bioavailability and serum half-life.
What was found
Both the 2 mg and 4 mg oral doses demonstrated an absolute bioavailability of approximately 15%. No difference in serum half-life was observed between any of the study phases. Exact numerical half-life values and variance metrics were not reported in the abstract.
Why it matters
This study establishes that oral melatonin tablets in standard low-to-moderate doses have poor systemic bioavailability (~15%) in humans, driven by poor absorption, first-pass metabolism, or a combination of both.
Limits
The trial had a small sample size of 12 healthy volunteers. The abstract does not provide exact numeric half-lives, clearance metrics, or variance measures, and doses above 4 mg were not evaluated to test for saturation of first-pass metabolism.
Cited by
- supports Between 70% and 90% of an oral melatonin dose is metabolized by the liver and kidney within one hour.