Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses.
OBJECTIVE
To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses.


METHODS
5 donkeys, 5 mules, and 3 horses.


METHODS
Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables.


RESULTS
Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses. In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours). Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys. Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys.


CONCLUSIONS
Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly, compared with horses. Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules.
Peck
Kenneth E
KE
Texas Veterinary Medical Center, Texas A&M University, College Station 77843-4474, USA.
Matthews
Nora S
NS
Taylor
Tex S
TS
Mealey
Katrina L
KL
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018397:Equidae / Q000378:metabolism*; D005260:Female; D006736:Horses / Q000378:metabolism*; D008297:Male; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000097:blood / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination