Disposition and excretion of 6-methoxy-2-naphthylacetic acid, the active metabolite of nabumetone in horses

L. R. Soma From the School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 W Street Rd. Kennett Square. PA 19348 (Soma), and Pennsylvania Equine Toxicology and Research Laboratory, Department of Chemistry, West Chester University, West Chester. PA 19383 (Uboh, Rudy. Smith).

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C. E. Uboh From the School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 W Street Rd. Kennett Square. PA 19348 (Soma), and Pennsylvania Equine Toxicology and Research Laboratory, Department of Chemistry, West Chester University, West Chester. PA 19383 (Uboh, Rudy. Smith).

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J. A. Rudy From the School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 W Street Rd. Kennett Square. PA 19348 (Soma), and Pennsylvania Equine Toxicology and Research Laboratory, Department of Chemistry, West Chester University, West Chester. PA 19383 (Uboh, Rudy. Smith).

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M. S. Smith From the School of Veterinary Medicine, University of Pennsylvania, New Bolton Center Campus, 382 W Street Rd. Kennett Square. PA 19348 (Soma), and Pennsylvania Equine Toxicology and Research Laboratory, Department of Chemistry, West Chester University, West Chester. PA 19383 (Uboh, Rudy. Smith).

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Abstract

Objective

To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone.

Design

Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA.

Procedure

Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV.

Results

Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-life of 0.88 hour. The elimination half-life was 11 hours. Area under the plasma concentration time curve for 6MNA after oral administration of nabumetone was 120.6 mg/h/L. A dose of 2.5 mg/kg of 6MNA administered IV resulted in plasma concentration nearly equivalent to that induced by the orally administered dose. Disposition of 6MNA was modeled as a one-compartment, first-order elimination. The area under the plasma concentration time curve for IV administration of 6MNA was 117.0 mg/h/L, and the specific volume of distribution was 0.247 L/kg. The distribution half-life and the elimination half-life were 0.56 and 7.90 hours, respectively. Percentage of total dose recovered in urine for the 36-hour collection period after the oral and IV administrations was 7.4 and 5.3%, respectively.

Conclusions

Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional metabolites of nabumetone in urine that could not be fully identified and characterized. (Am J Vet Res 1996;57:517–521)

Abstract

Objective

To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone.

Design

Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA.

Procedure

Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV.

Results

Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-life of 0.88 hour. The elimination half-life was 11 hours. Area under the plasma concentration time curve for 6MNA after oral administration of nabumetone was 120.6 mg/h/L. A dose of 2.5 mg/kg of 6MNA administered IV resulted in plasma concentration nearly equivalent to that induced by the orally administered dose. Disposition of 6MNA was modeled as a one-compartment, first-order elimination. The area under the plasma concentration time curve for IV administration of 6MNA was 117.0 mg/h/L, and the specific volume of distribution was 0.247 L/kg. The distribution half-life and the elimination half-life were 0.56 and 7.90 hours, respectively. Percentage of total dose recovered in urine for the 36-hour collection period after the oral and IV administrations was 7.4 and 5.3%, respectively.

Conclusions

Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional metabolites of nabumetone in urine that could not be fully identified and characterized. (Am J Vet Res 1996;57:517–521)

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