Pharmacokinetics and bioavailability of trimethoprim‐sulfamethoxazole in alpacas

The pharmacokinetics and bioavailability of trimethoprim‐sulfamethoxazole (TMP‐SMX) were studied in six healthy male‐castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP‐SMX using a crossover design with a 2‐week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP‐SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP‐SMX. After i.v. administration of 15 mg/kg of TMP‐SMX the mean initial plasma concentration (C0) was 10.75 ± 2.12 μg/mL for trimethoprim (TMP) and 158.3 ± 189.3 μg/mL for sulfamethoxazole (SMX). Elimination half‐lives were 0.74 ± 0.1 h for TMP and 2.2 ± 0.6 h for SMX. The mean residence times were 1.45 ± 0.72 h for TMP and 2.8 ± 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 ± 1.62 μg h/mL for TMP and 124 ± 60 μg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 ± 9.85 and 1.90 ± 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 ± 1.15 L/kg for TMP and 0.35 ± 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 ± 0.8, 2.6 ± 0.4 and 2.8 ± 0.7 μg/mL, respectively. The AUC was 9.1 ± 5, 25.9 ± 3.3 and 39.1 ± 4.1 μg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP‐SMX are not achieved after p.o. administration to alpacas.