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Pharmacokinetics and bioavailability of trimethoprim‐sulfamethoxazole in alpacas
Author(s) -
Chakwenya J.,
Lakritz J.,
Tyler J.,
Fales W. H.,
JamesKracke M.,
Smith K.,
Holle J.
Publication year - 2002
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.2002.00425.x
Subject(s) - bioavailability , pharmacokinetics , trimethoprim , volume of distribution , chemistry , sulfamethoxazole , pharmacology , oral administration , zoology , medicine , antibiotics , biochemistry , biology
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 ( C 0 ) 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 ( Cl t ) 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 ( C max ) 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.