Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection
- 228 Downloads
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 μg/person and after a 5 h infusion of 20 μg 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 β 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.
Key wordsMelatonin Pharmacokinetics replacement therapy
Unable to display preview. Download preview PDF.
- Aldhous M, Franey C, Wright J, Arendt J (1985) Plasma concentrations of melatonin in man following oral absorption of different preparations. Br J Clin Pharmacol 19: 517–521Google Scholar
- Brun J, Claustrat B, Harthe C, Vitte PA, Cohen R, Chazot G (1985) Melatonin radioimmunoassay. Analytical and physiological criteria of validity. In Brown GM, Wainwright SD (eds) The pineal gland: Endocrine aspects. Advances in the biosciences. Pergamon, vol 53, pp 41–45Google Scholar
- Cazin JL, Luyckx M (1984) Determination of pharmacokinetic parameters on the Apple computer. Trends Pharmacol Sci 5: 1214–1216Google Scholar
- Chazot G, Claustrat B, Brun J, Jordan D, Sassolas G, Schott B (1984) A chronobiological study of melatonin, cortisol, growth hormone and prolactin secretion in cluster headache. Cephalalgia 4: 213–220Google Scholar
- Claustrat B, Chazot G, Brun J, Jordan D, Sassolas G (1984) A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry 19: 1215–1228Google Scholar
- Claustrat B, Loisy C, Brun J, Beorchia S, Arnaud JL, Chazot G (1989) Nocturnal plasma melatonin levels in migraine: a preliminary report. Headache 29: 241–244Google Scholar
- Claustrat B, Le Bars D, Brun J, Thivolle P, Mallo C, Arendt J, Chazot G (1989) Plasma and brain pharmacokinetic studies after intravenous administration of cold or 11C labelled melatonin. In: Reiter RJ, Pang SF (eds) Advances in Pineal Research, vol 3: Libbey, London, pp 305–310Google Scholar
- Ekins RP (1981) The “precision profile”: its use in RIA assessment and design. Ligand Quart 33: 4–10Google Scholar
- Gibaldi M, Perrier D (1982) Pharmacokinetics. Swarbrick J. (ed.) Drugs and the pharmaceutical sciences, vol. 15. Dekker, New York, p 60Google Scholar
- Iguchi H, Kato KI, Ibayashi H (1982) Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab 54: 1025–1027Google Scholar
- Lane EA, Moss HB (1985) Pharmacokinetics of melatonin in man: first pass hepatic metabolism. J Clin Endocrinol Metab 61: 1214–1216Google Scholar
- Ross JL, Barnes KM, Brody S, Merriam GR, Loriaux DL, Cutler GB (1984) A comparison of two methods for detecting hormone peaks: the effect of sampling interval on gonadotropin peak frequency. J Clin Endocrinol Metab 59: 1159–1163Google Scholar
- Tillement JP (1978) The relationship between plasma protein binding distribution and pharmacokinetics of drugs. In: Tillement JP (ed) Advances in Pharmacology and Therapeutics. Vol 7. Pergamon, Oxford, pp 103–111Google Scholar
- Vakkuri O, Leppaluoto J, Karuppila A (1985) Oral administration and distribution of melatonin human serum, saliva and urine. Life Sci 37: 489–495Google Scholar
- Waldhauser F, Waldhauser M, Lieberman HR, Reng MH, Lynch HJ, Wurtman J (1984) Bioavaibility of oral melatonin in humans. Neuroendocrinol 39: 307–313Google Scholar
- Wood JH, Lee AJ, Garrettson LK (1979) Periodicity during the distributive phase for drugs administered intravenously to humans. Drug Metab Rev 9: 119–128Google Scholar