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Pharmacokinetics of multiple-dose administration of eltenac in horses
T M Dyke1, R A Sams, K G Thompson
1Analytical Toxicology Laboratory, College of Veterinary Medicine, The Ohio State University, Columbus 43210-1089, USA.
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 microg.h/ml (range, 5.61 to 8.08 microg.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 microg.h/ml (range, 5.21 to 7.44 microg.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 microg/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.