Prednisolone Pharmacokinetics in Dogs with Protein-losing Enteropathy

Background – Approximately 50% of dogs with protein-losing enteropathy (PLE) do not improve in response to orally administered steroids. It is unknown if steroid malabsorption contributes to treatment failures.

Objective-To compare pharmacokinetics of orally administered prednisolone in dogs with PLE versus healthy controls (HC). 
Animals – Fourteen dogs with PLE and 7 control dogs.
 Methods – Prospective case-controlled study. Dogs treated with 1 mg/kg prednisolone PO once daily for approximately 3 weeks. Blood samples collected at set timepoints before and after prednisolone administration on first (T1= day 1) and final (T2) study days. Total and non-protein bound prednisolone concentrations determined with LC-MS-MS, and data subjected to non-compartmental analyses. Pharmacokinetics variables compared between PLE and control dogs and between PLE short-term responders and non-responders. 

Results – PLE dogs had a shorter elimination half-life (mean ± SD) than control dogs (1.4 ± 0.4 hours vs. 1.8 ± 0.3; P = .05) whereas the percentage of non-protein bound serum prednisolone (median, interquartile range) was higher in PLE dogs versis control dogs (15.7%, 7.5-22.1% vs 6.7%, 5.4-8.8%; 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 – Overall drug exposures are similar between PLE dogs and healthy controls. Steroid malabsorption is unlikely to be a common cause of treatment failure in dogs with PLE.