Although carnitine has been found in bile, the role of biliary excretion in neonatal carnitine homeostasis is unclear. Infants receiving MCT exhibit characteristic acylcarnitines in blood and urine and may develop carnitine deficiency (Ishida et al., Tohoku J Exp Med 1994;172:59). To evaluate the potential contribution of biliary excretion to neonatal carnitine loss in the presence and absence of dietary MCT, 2-week-old piglets were equipped with central venous, upper jejunal, common bile duct and bladder catheters. Following recovery from surgery, the piglets were enterally fed via jejunal catheter on subsequent days with: Day 1) sow-milk substitute; Day 2) the same supplemented with 10 g/kg MCT oil; Days 3 and 4) sow-milk substitute. Blood samples and 24-hr collections of bile and urine were obtained for measurement of free and esterified carnitine (including radioisotopic exchange-HPLC detection of individual carnitine esters). Bile was re-fed every 8 hours. Results: Biliary excretion of total carnitine averaged 10.6μmol/24 hr compared with a mean urinary loss of 35.7 μmol/24 hr. Carnitine was esterified to a greater extent in the bile than in urine or blood (86.4% vs. 59.4% and 14.4%, respectively). Acetylcarnitine was the major acylcarnitine detected in the bile during feedings with sow-milk substitute. MCT administration was associated with a 60% increase in bile flow and the appearance of medium chain acylcarnitines (C6>C8>C10) in the bile. Bile flow rate and acylcarnitine profile returned to basal status within 48 hours after stopping MCT feeding. The biliary excretion of carnitine esters probably reflects an MCT-induced metabolic challenge to the liver and represents a detoxification mechanism. It is unclear how much biliary carnitine is reabsorbed from the intestine. However, since only about 20% of dietary carnitine is thought to be absorbed, biliary excretion could represent a previously unrecognized, but potentially significant pathway for carnitine loss from the body that may be accentuated by dietary factors such as MCT.(Funded by USPHS HD29273)