Prednisolone pharmacokinetics in dogs with protein-losing enteropathy.

Abstract

BACKGROUND: It is unknown if glucocorticoid malabsorption contributes to the approximate 50% treatment failure rate in dogs with protein-losing enteropathy (PLE). OBJECTIVE: To compare pharmacokinetics (PK) of orally administered prednisolone in dogs with PLE vs healthy controls. ANIMALS: Fourteen dogs with well-characterized PLE and 7 control dogs. METHODS: Prospective case-controlled study. Dogs were treated with 1 mg/kg prednisolone PO once daily for approximately 3 weeks. Venous blood samples were collected at set timepoints before and after prednisolone administration on the first (T1) and final (T2) study days. Total and non-protein bound serum prednisolone concentrations were determined using liquid chromatography tandem-mass spectrometry, and pharmacokinetics variables were derived from the drug concentration data. Pharmacokinetics variables were compared between PLE and control dogs and between PLE short-term responders and non-responders. RESULTS: The PLE dogs had a shorter half-life of the terminal slope than control dogs (harmonic mean of 1.3 vs 1.8 hours; P = .05) whereas the percentage of serum prednisolone that was non-protein bound was higher in PLE dogs than in control dogs (median of 15.7% vs 6.7%; P = .02) at T1. Total prednisolone drug exposures and maximum total serum drug concentrations did not differ between PLE and control dogs at T1 or T2, nor did they differ between short-term responders and non-responders within the PLE population (P > .05 for all comparisons). CONCLUSIONS AND CLINICAL IMPORTANCE: Overall drug exposures are similar between PLE dogs and healthy controls. Glucocorticoid malabsorption is unlikely to be a common cause of treatment failure in dogs with PLE.