Diurnal Rhythm of Melatonin in Bovine Milk: Pharmacokinetics of Exogenous Melatonin in Lactating Cows and Goats

Abstract

We investigated whether the melatonin levels in bovine milk exhibit a similar daily rhythm as serum levels. In 4 Ayr-shire cows at the beginning of the lactation period in May the nocturnal rise in milk melatonin was moderate (from 7 ± 2 pg/ml at noon to 15 ± 1 pg/ml at night; mean ± SEM) and did not correlate well with the melatonin level in serum (from 7 ± 2 pg/ml to 27 ± 7 pg/ml, respectively). On the other hand, 6 cows in a later phase of lactation, studied in February, showed a clear long-lasting nocturnal melatonin increase both in serum (from 9 ± 1 pg/ml at noon to 26 ± 3 pg/ml at night) and in milk (from 12 ± 5 pg/ml to 26 ± 7 pg/ml, respectively). Melatonin kinetics during lactation was studied in more detail in 4 Ayrshire cows and 4 dairy goats by giving an intravenous bolus injection of melatonin. A 3-compartment model with melatonin elimination from the central compartment was used to describe the data. The values (mean ± SD) for the cows and the goats were: elimination half-life 27 ± 4 min and 27 ± 1 min, mean residence time 24 ± 4 min and 18 ± 4 min, steady state distribution volume 1.0 ± 0.3 1/kg and 0.6 ± 0.1 1/kg (p<0.05), and plasma clearance 0.044 ± 0.004 1/kg/min and 0.035 ±0.011 1/kg/min, respectively. Following injection, the melatonin concentration in milk increased rapidly and exceeded the corresponding serum value 15-30 min later, remaining thereafter above the serum level. Our results suggest that milk melatonin levels reflect blood concentrations of melatonin with a short delay.