Serum and skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs

Heidy Ortiz Pohlenz-Zertuche From the Department of Small Animal Clinical Sciences (Pohlenz-Zertuche, Kunkle) and Large Animal Clinical Sciences (Brown, Gronwall) College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Murray P. Brown From the Department of Small Animal Clinical Sciences (Pohlenz-Zertuche, Kunkle) and Large Animal Clinical Sciences (Brown, Gronwall) College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Ronald Gronwall From the Department of Small Animal Clinical Sciences (Pohlenz-Zertuche, Kunkle) and Large Animal Clinical Sciences (Brown, Gronwall) College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Gail A. Kunkle From the Department of Small Animal Clinical Sciences (Pohlenz-Zertuche, Kunkle) and Large Animal Clinical Sciences (Brown, Gronwall) College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Kelly Merritt From the Department of Small Animal Clinical Sciences (Pohlenz-Zertuche, Kunkle) and Large Animal Clinical Sciences (Brown, Gronwall) College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Summary

Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (sdz) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of tmp and sdz were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum tmp concentration was 0.67 ± 0.02 μg/ml, and mean skin tmp concentration was 1.54 ± 0.40μg/g. Mean serum sdz concentration was 51.1 ± 12.2 μg/ml and mean skin sdz concentration was 59.3 ± 9.8 μg/g. In experiment 2, mean serum tmp concentration was 1.24 ± 0.35 μg/ml and mean skin tmp concentration was 3.03 ± 0.54 μg/g. Mean serum SDZ concentration was 51.6 ± 9.3 μg/ml and mean skin sdz concentration was 71.1 ± 8.2 μg/g. After the 5th oral dose in both experiments, mean concentration of tmp and sdz in serum and skin exceeded reported minimal inhibitory concentrations of tmp/sdz (≤ 0.25/4.75 μg/ml) for coaguase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer’s recommended dosage of 30 mg of tmp/sdz/kg (5 mg of TMP/kg and 25 mg of sdz/kg) every 24 hours.

Summary

Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (sdz) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of tmp and sdz were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum tmp concentration was 0.67 ± 0.02 μg/ml, and mean skin tmp concentration was 1.54 ± 0.40μg/g. Mean serum sdz concentration was 51.1 ± 12.2 μg/ml and mean skin sdz concentration was 59.3 ± 9.8 μg/g. In experiment 2, mean serum tmp concentration was 1.24 ± 0.35 μg/ml and mean skin tmp concentration was 3.03 ± 0.54 μg/g. Mean serum SDZ concentration was 51.6 ± 9.3 μg/ml and mean skin sdz concentration was 71.1 ± 8.2 μg/g. After the 5th oral dose in both experiments, mean concentration of tmp and sdz in serum and skin exceeded reported minimal inhibitory concentrations of tmp/sdz (≤ 0.25/4.75 μg/ml) for coaguase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer’s recommended dosage of 30 mg of tmp/sdz/kg (5 mg of TMP/kg and 25 mg of sdz/kg) every 24 hours.

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