The metabolism of arylazoisoxazolones by rats and dogs.
1. When rats were given a single oral dose of the lipid-soluble fungicide 4-(2-chlorophenylhydrazono)-3-methyl[4-(14)C]isoxazol-5-one ([(14)C]drazoxolon), about 75% of the label was excreted in the urine and 13% in the faeces in 96hr. An additional 7% of the radioactivity was recovered as (14)CO(2) in 48hr. 2. About 8% of the label was excreted by rats in the bile in 0-24hr. and an additional 6% was excreted by the same route in 24-48hr. 3. When dogs were given a single oral dose of [(14)C]drazoxolon about 35% of the label was excreted in the urine and a similar amount was excreted in the faeces in 96hr. 4. The major metabolites in the urine of the rat and the dog were identified as 2-(2-chloro-4-hydroxyphenylhydrazono)acetoacetic acid (dog, 14%), the corresponding ether glucosiduronic acid (dog, 12%; rat, 13%) and ester sulphate (rat, 65%). 5. When rats were given a single oral dose of 3-methyl-4-([U-(14)C]phenylhydrazono)isoxazol-5-one about 75% of the label was excreted in the urine and 15% in the faeces in 96hr. The major metabolite in the urine was identified as the ester sulphate conjugate of 2-(4-hydroxyphenylhydrazono)-acetoacetic acid. 6. Reduction of the azo link was of minor quantitative significance. 7. These results are discussed in their relation to species differences in the toxicity of these compounds.
D000090:Acetoacetates / Q000652:urine; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism*; D001646:Bile / Q000032:analysis; D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D004285:Dogs; D005243:Feces / Q000032:analysis; D005965:Glucuronates / Q000652:urine; D008297:Male; D010080:Oxazoles / Q000378:metabolism*; D051381:Rats; D013431:Sulfates / Q000652:urine
D000090:Acetoacetates; D000935:Antifungal Agents; D002247:Carbon Isotopes; D005965:Glucuronates; D010080:Oxazoles; D013431:Sulfates; D002245:Carbon Dioxide