Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection

Abstract

The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished was investigated after the i.v. infusion--once during the night and once during the day. The clearance of melatonin from blood showed a biexponential decay. The pharmacokinetic parameters in the two studies were similar, except for the disappearance rate constant beta and the apparent volume of distribution at steady-state (Vss). Supplementary peaks or troughs were superimposed on the plateau and the falling part of the profile. They were not due to stimulation of endogenous secretion, because they were also seen in the pinealomectomized patient. During the melatonin infusion, the plasma hormone level reached a steady-state after 60 and 120 min, and when it was equal to the nocturnal level. The infusion regime may be valuable in replacing blunted hormonal secretion in disease states.

Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

“…Exogenously administered melatonin has a short half life (20-60 min) with a high hepatic first pass effect [32,33]. The major metabolites of fluvoxamine (65%) are produced by oxidative demethylation of the aliphatic methoxyl group of the parent compound [34].…”

Solid Lipid Nanoparticles Incorporating Melatonin as New Model for Sustained Oral and Transdermal Delivery Systems

“…For clinical purposes, exogenous MT administration should be able to mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable. After an intravenous bolus injection MT half-life of elimination is very short (about 40 min) 8 and, when administer orally, MT shows low bioavailability and a rapid clearance from plasma influenced by a marked firs pass hepatic metabolism.…”

Melatonin and its therapeutic actions on peripheral nerve regeneration

“…It has been reported that plasma melatonin levels reached a steady-state after 60 min and 120 min after melatonin administration [30]. In another study, the maximal mean serum melatonin value reached 20 min after a single subcutaneous injection of melatonin in hamsters [57].…”