EFFICACY OF 4-METHYLPYRAZOLE FOR TREATMENT OF ETHYLENE-GLYCOL INTOXICATION IN DOGS

4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was admin istered to dogs to treat ethylene glycol (EG) intoxication. Eleven dog s were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 ho urs after EG ingestion. 4-Methylpyrazole was administered IV as a 50-m g/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 1 2 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, bioch emical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 h ours, and at 1 week and 2 weeks after EG ingestion. Dogs of both group s developed clinicopathologic signs associated with EG intoxication, i ncluding cnrs depression, hyperosmolality, high anion gap metabolic ac idosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrat e crystalluria, and isosthenuria. Fractional excretion of sodium was i ncreased in all dogs between 1 and 9 hours after EG ingestion, but rem ained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. AU dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical , or clinical evidence of renal impairment. Of the 6 dogs treated 8 ho urs after EG ingestion, 2 developed acute renal failure. One of the do gs treated 8 hours after EG ingestion remained isosthenuric for 2 mont hs, but did not manifest any other signs of renal impairment. Of the d ogs treated 8 hours after EG ingestion, 3 recovered without morphologi c, biochemical, or clinical evidence of renal impairment. Serum half-l ife of EG was prolonged in the dogs treated 8 hours after EG ingestion . Percentage of EG excreted unchanged was 84 +/- 2% in the dogs treate d 5 hours after EG ingestion, and was 40 +/- 10% in the dogs treated 8 hours after EG ingestion. 4-Methylpyrazole was effective in preventin g renal failure in all dogs given 10.6 g of EG/kg when treatment was i nitiated by 5 hours after EG ingestion, and in 4 of 6 dogs when treatm ent was initiated by 8 hours after EG ingestion.