COMPARATIVE PHARMACOKINETICS OF TRIMETHOPRIM-SULFAMETHOXAZOLE ADMINISTERED INTRAVENOUSLY AND ORALLY TO CAPTIVE ELEPHANTS

Three healthy captive female African elephants (Loxodonta africana) were used to determine the pharmacokinetics of trimethoprim-sulfamethoxazole (TMP-SMZ) after a single i.v. and a single oral dose of 3.7 mg/kg TMP and 18.3 mg/kg SMZ. A 2-mo wash-out period was allowed between the i.v. and oral trials. An adult female Asian elephant (Elephas maximus) was also used in this investigation; however, pharmacokinetic parameters calculated from data from this animal were not used to calculate mean pharmacokinetic parameters for TMP-SMZ in African elephants. Serum concentrations of TMP-SMZ were measured by high-performance liquid chromatography on blood samples collected via venous catheterization predose, and over 12 hr after i.v. drug administration, and over 24 hr after oral drug administration. For African elephants, the mean terminal half-life (i/2 z), clearance (CL), and volume of distribution at steady state (Vdss) of TMP following i.v. administration were 1.4 ? 0.7 hr, 856.0 ? 144.0 ml/hr/kg, and 1.1 ? 0.4 L/kg, respectively. For SMZ, these parameters were 1.83 ? 0.06 hr, 93.6 ? 10.8 ml/hr/kg, and 0.2 ? 0.02 L/kg, respectively. Following oral administration, the mean t,/2z was 3.0 ? 1.1 hr, the maximum concentration (Cmax) was 0.43 ? 0.07 ?xg/m at time (tmax) 1.7 ? 0.6 hr, and the bioavailability (F) was 61.2 ? 21.3% for TMP. For SMZ, the mean t/2,z was 2.0 ? 0.3 hr, the Cmax was 30.7 ? 2.5 fig/ ml at tmax 3.0 ? 1.0 hr, and F was 81.7 ? 17.5%. Calculated pharmacokinetic parameters from this investigation were similar to values reported in horses. Based on these findings, metabolic scaling