Ursodeoxycholic Acid Oral Pharmacokinetics and Plasma Bile Acid Profile Changes in a Population of Healthy Neonatal Foals.

Abstract

Ursodeoxycholic acid (UDCA) is a secondary bile acid used in humans for the treatment of some cholestatic diseases. Interest in its potential use in equine patients with liver conditions has increased. Pharmacokinetic parameters in adult horses have recently been reported; however, they are not available for foals. The objective of this study was to characterize the pharmacokinetics of UDCA following a single oral dose of 15 mg/kg in six healthy neonatal foals and evaluate associated changes in bile acids (BA) profile. UDCA concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis demonstrated median peak concentration (Cmax) of 23.74 μmol (range 12.86-38.02 μmol) obtained at 5.5 h (range 2-6 h) (Tmax). Concentrations declined by 24 h post-dosing, with minimal levels detected between 48 and 72 h. The median half-life was calculated to be 10.32 h (range 8.05-19.12 h), and the estimated mean dosing interval was approximately 12 h. Following administration, plasma UDCA concentrations increased substantially, with marked shift in BA profiles resulting in an increase in the proportion of UDCA relative to other BAs. These results suggest that an oral UDCA dose of 15 mg/kg administered every 12 h is likely appropriate for neonatal foals.