Antipyrine pharmacokinetics and urinary excretion in female horses

T. M. Dyke From the Analytical Toxicology Laboratory and Equine Exercise Physiology Laboratory, College of Veterinary Medicine, The Ohio State University, 601 Vernon L Tharp St, Columbus, OH 43210-1089.

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 BVSc, MVSc, PhD
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R. A. Sams From the Analytical Toxicology Laboratory and Equine Exercise Physiology Laboratory, College of Veterinary Medicine, The Ohio State University, 601 Vernon L Tharp St, Columbus, OH 43210-1089.

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 PhD
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K. W. Hinchcliff From the Analytical Toxicology Laboratory and Equine Exercise Physiology Laboratory, College of Veterinary Medicine, The Ohio State University, 601 Vernon L Tharp St, Columbus, OH 43210-1089.

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 BVSc, MS, PhD

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Abstract

Objective

To measure renal clearance of antipyrine and urinary excretion of antipyrine (AP) metabolites in horses by use of validated high-performance liquid chromatography (HPLC) methods.

Animals

8 Standardbred mares.

Procedure

HPLC methods for measurement of AP in equine plasma and AP and its metabolites in equine urine were validated. Antipyrine (20 mg/kg of body weight) was administered IV, and blood samples and urine specimens were collected over 24 hours.

Results

Median plasma clearance of AP in horses was 6.2 ml/min/kg, of which < 2% could be attributed to renal clearance. Urinary excretion of AP and its metabolites over 24 hours accounted for < 22% of the AP dose administered. The major metabolite of AP in urine was 4-hydroxyantipyrine.

Conclusions and Clinical Relevance

Use of the proven validated methods for measuring AP and its metabolites indicated that AP has minimal renal clearance in horses, suggesting that plasma clearance of AP reflects hepatic clearance. Combined with AP metabolite data, the pharmacokinetics of AP may be useful for assessment of hepatic cytochrome P450 activity in horses. (Am J Vet Res 1998;59:280–285)

Abstract

Objective

To measure renal clearance of antipyrine and urinary excretion of antipyrine (AP) metabolites in horses by use of validated high-performance liquid chromatography (HPLC) methods.

Animals

8 Standardbred mares.

Procedure

HPLC methods for measurement of AP in equine plasma and AP and its metabolites in equine urine were validated. Antipyrine (20 mg/kg of body weight) was administered IV, and blood samples and urine specimens were collected over 24 hours.

Results

Median plasma clearance of AP in horses was 6.2 ml/min/kg, of which < 2% could be attributed to renal clearance. Urinary excretion of AP and its metabolites over 24 hours accounted for < 22% of the AP dose administered. The major metabolite of AP in urine was 4-hydroxyantipyrine.

Conclusions and Clinical Relevance

Use of the proven validated methods for measuring AP and its metabolites indicated that AP has minimal renal clearance in horses, suggesting that plasma clearance of AP reflects hepatic clearance. Combined with AP metabolite data, the pharmacokinetics of AP may be useful for assessment of hepatic cytochrome P450 activity in horses. (Am J Vet Res 1998;59:280–285)

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