Pharmacokinetics of multiple-dose administration of eltenac in horses

T. M. Dyke From the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus OH 43210-1089 (Dyke, Sams, Ashcraft); and Schering-Plough Animal Health, 1095 Morris Ave, Union NJ 07083 (Thompson).

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R. A. Sams From the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus OH 43210-1089 (Dyke, Sams, Ashcraft); and Schering-Plough Animal Health, 1095 Morris Ave, Union NJ 07083 (Thompson).

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K. G. Thompson From the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus OH 43210-1089 (Dyke, Sams, Ashcraft); and Schering-Plough Animal Health, 1095 Morris Ave, Union NJ 07083 (Thompson).

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S. M. Ashcraft From the Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus OH 43210-1089 (Dyke, Sams, Ashcraft); and Schering-Plough Animal Health, 1095 Morris Ave, Union NJ 07083 (Thompson).

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Abstract

Objective

To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule.

Animals

6 adult mares.

Procedure

Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography.

Results

On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 μg•h/ml (range, 5.61 to 8.08 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 μg•h/ml (range, 5.21 to 7.44 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 μg/ml.

Conclusion

Pharmacokinetic variables determined for each horse were not different between days 0 and 4.

Clinical Relevance

Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac. (Am J Vet Res 1998;59:1447–1450)

Abstract

Objective

To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule.

Animals

6 adult mares.

Procedure

Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography.

Results

On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 μg•h/ml (range, 5.61 to 8.08 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 μg•h/ml (range, 5.21 to 7.44 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 μg/ml.

Conclusion

Pharmacokinetic variables determined for each horse were not different between days 0 and 4.

Clinical Relevance

Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac. (Am J Vet Res 1998;59:1447–1450)

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