Background Evidence from neonatal studies is critical in understanding developmental variations in drug pharmacokinetics and can guide dosing adjustments. Melatonin has been shown previously in a single dose study to have slow clearance and prolonged half-life in preterm infants.
Aim To determine the melatonin pharmacokinetic profile in preterm infants on exogenous supplementation and to determine the melatonin concentrations in donor and maternal breast milk.
Methods The study was part of an exploratory; double-blinded randomised placebo controlled trial evaluating the neuroprotective effect of melatonin in preterm infants less than 31 weeks gestation. Infants in the melatonin arm (n = 29) received an intravenous infusion 0.1 mcg/kg/hr for 2 h once daily for 7 days starting by 48 h after birth. The placebo group (n = 28) received same volume of saline. Plasma and milk melatonin concentrations were analysed by radioimmunoassay. Population pharmacokinetics was carried out using NONMEM.
Results The median plasma melatonin levels on day 4 was 152pg/ml in the melatonin group and was 0pg/ml in the saline group. On nonlinear mixed effect modelling, using first order conditional estimation with interaction, the clearance was 0.05L/hr with a half-life of 15.61 h. Effect of covariates: gender and race were not significant in this study unlike previously reported. Mean melatonin concentrations in donor breast milk were 63pg/ml, higher than that of maternal breast milk even on day 4 (16.6 pg/ml).
Conclusions Preterm infants have delayed clearance and prolonged half-life of melatonin. This data can be used for simulation of future dose studies in preterm infants.