2015 ACVIM Forum Research Abstract Program

Five healthy beagle dogs were given a single IV dose of 24 mg/kg, of meropenem, and received IHD. IHD initiated at the end of infusion of meropenem, and FX paed was used as artificial kidney. Blood flow rate was 40 mL/min. Dialysate flow rate and ultrafiltration rate were 300 mL/min and 40 mL/h respectively. Blood samples were collected for 24 hours from jugular vein, extracorporeal arterial and venous line. Urine samples and dialysate were collected. Concentrations of meropenem were measured using HPLC/MS/MS determination. Pharmacokinetic data and simulation of dosing regimen were analyzed by WinNolin 4.1 program. Mean peak plasma concentration was 116 AE 37 mg at 15 minute. Mean total body clearance was 347 AE 117 mL/h/kg and mean steady state volume of distribution was 223 AE 67 L/kg. Approximately 69% of administered drug was excreted by urine in unchanged form. Dialysis clearance was 75 AE 23 mL/h/kg and extraction ratio of dialysis was 0.46 AE 0.09. Half-life of meropenem in dogs with renal failure was prolonged by 2-fold compared to the dogs with renal failure receiving IHD. In conclusion, 21% meropenem was removed from the dogs through dialysis. Based on the simulated data, additional dose of 24 mg/kg of meropenem after dialysis is suggested. We have recently shown that serum symmetric dimethylarginine (SDMA) is a biomarker for canine and feline CKD, which is earlier than serum creatinine, using a highly sensitive and specific liquid chromatography-mass spectrometry LC-MS analytical method which was validated per FDA and CLIA guidelines. This report describes a high throughput immunoassay that has been developed and correlated to the gold standard LC/MS assay.