DISPOSITION AND EXCRETION OF 6-METHOXY-2-NAPHTHYLACETIC ACID, THE ACTIVE METABOLITE OF NABUMETONE IN HORSES

Objective-To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonste roidal anti-inflammatory prodrug nabumetone. Design-Pharmacokinetic an alysis of 6MNA after oral administration of nabumetone and IV administ ration of 6MNA. Procedure-Using a crossover design, 5 horses were oral ly 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. Res ults-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 concentrati on 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 pla sma concentration nearly equivalent to that induced by the orally admi nistered dose. Disposition of 6MNA was modeled as a one-compartment, f irst-order elimination. The area under the plasma concentration time c urve 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. Perc entage of total dose recovered in urine for the 36-hour collection per iod after the oral and IV administrations was 7.4 and 5.3%, respective ly. Conclusions-Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional met abolites of nabumetone in urine that could not be fully identified and characterized.