PHARMACOKINETICS OF MELATONIN IN HUMAN SEXUAL-MATURATION

To determine whether melatonin pharmacokinetics change during puberty, we infused melatonin iv in 9 prepubertal, 8 pubertal, and 16 adult su bjects and measured melatonin in serum and saliva, and 6-hydroxymelato nin sulfate in urine. A pilot study of 3 adult males showed dose linea rity, absence of saturation kinetics, and unaltered metabolism and uri nary excretion for doses of 0.1, 0.5, and 5.0 mu g/kg. All other subje cts received 0.5 mu g/kg melatonin. The results of pharmacokinetic par ameters calculated from serum melatonin showed no significant gender d ifferences in adults. However, developmental differences were signific ant between prepubertal children and adults for terminal elimination r ate constant(1.08 +/- 0.25 us. 0.89 +/- 0.11 h(-1)), elimination half- life (0.67 +/- 0.12 vs. 0.79 +/- 0.10 h), and area under the concentra tion-time curve (250.9 +/- 91.8 vs. 376.9 +/- 154.3 (pg/mL). h, respec tively). At all time points melatonin levels were higher in serum than in saliva, and the ratio between serum and salivary melatonin varied up to 55-fold within and between individuals. Results based on salivar y melatonin showed significant differences between prepubertal childre n and adults for the terminal elimination rate constant (1.90 +/- 0.95 us. 1.06 +/- 0.28 h(-1)). The described group differences in pharmaco kinetic parameters suggest that prepubertal children metabolize melato nin faster than adults. The inconsistent ratio between serum and saliv ary melatonin calls for caution in the use of salivary melatonin for p harmacokinetic studies or to infer pineal function. The present findin gs, suggestive of faster melatonin metabolism in prepubertal children, combined with the known decline of serum melatonin with age and highe r excretion rate of the metabolite in prepubertal children lead us to conclude that the prepubertal pineal gland has a higher melatonin secr etion rate than the adult gland.