Despite methodological differences between the included studies, Tmax was approximately 50 min following oral immediate-release formulations of melatonin. T1/2 was 45 min in both administration routes. Cmax, AUC, Cl, and VD varied extensively between studies. Bioavailability of oral melatonin was approximately 15%.

BackgroundThe aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers.MethodsThe study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by “the method of residuals” and compartmental analysis. The pharmacokinetic variables: ka, t1/2 absorption, tmax, Cmax, t1/2 elimination,AUC0-∞, and bioavailability were determined for oral melatonin. Cmax, t1/2 elimination, Vd, CL and AUC0-∞ were determined for intravenous melatonin.ResultsTwelve male volunteers completed the study. Baseline melatonin plasma levels did not differ significantly between the study days (P = 0.067). Mean (SD) t1/2 absorption of oral melatonin was 6.0 (3.1) min. Mean tmax was 40.8 (17.8) min with a median (IQR) Cmax of 3550.5 (2500.5–8057.5) pg ml-1. Mean t1/2 elimination was 53.7 (7.0) min. Median absolute bioavailability was 2.5 (1.7–4.7) %. Median Cmax after short iv infusion of melatonin was 389,875.0 (174,775.0–440,362.5) pg ml-1. Mean t1/2 elimination was 39.4 (3.6) min, mean Vd 1.2 (0.6) l kg-1 and mean CL 0.0218 (0.0102) l min-1 kg-1.ConclusionsThis cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %.Trial registrationEudra-CT number: 2013-000205-23 (initial registration 27.03.2013).Clinicaltrials.gov Identifier: NCT01923974 (initial registration 08.08.2013).

These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration.