Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection.

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.