SAIM Resident III Colorado State University FORT COLLINS, CO, United States
Background - Previous research has shown that azotemic dogs have a lower clearance and higher drug plasma concentrations of ampicillin compared to healthy dogs. Hypothesis/objectives - Determine the pharmacokinetics of ampicillin after multiple intravenous doses in hospitalized azotemic and non-azotemic dogs. Animals - Thirty client-owned dogs; 20 azotemic and 10 non-azotemic. Methods - Prospective study. Ampicillin-sulbactam 22 mg/kg intravenously every 8 hours for up to 5 days. Blood samples were obtained at baseline, 1, 4, and 8 hours post-ampicillin administration each day. Plasma ampicillin was measured using LCMS and non-compartmental pharmacokinetic modeling and dose interval modeling were performed. Results - Plasma ampicillin exposure (azotemic mean 206.1 ug/ml x hr +/- 113.5, non-azotemic mean 60.3 +/- 35.7; p < 0.0009) and half-life (azotemic mean 3.8 hours +/- 2.3, non-azotemic mean 1.5 hours +/- 0.3; p < 0.00001) were statistically greater in azotemic dogs compared to non-azotemic dogs. Single dose interval modeling showed that 75% of azotemic dogs had > 50% time>MIC (MIC = 8) with q12 hour dosing (85% with q8) whereas no non-azotemic dogs had > 50% time>MIC (MIC = 8) with q12 hour dosing (10% with q8). On day 3, 67% of azotemic dogs had at least 50% time>MIC (MIC =8) with q12 hour dosing (78% with q8). Conclusion and clinical importance - Azotemic dogs have significantly higher ampicillin drug exposure and half-life. Over multiple days of hospitalization, the majority of azotemic dogs continued to have greater than 50% time>MIC (MIC=8) at q12 hour dosing.
