1991 Volume 16 Issue 2 Pages 211-221
On single oral administration of (S), (E)-1-(p-chlorophenyl)-4, 4-dimethyl-2-(1, 2, 4-triazol-1-yl)-1-penten-3-ol [designated as (S)-E], a main ingredient of uniconazole, labeled with 14C at the triazole ring at dose levels of 1 and 200mg/kg to male and female rats, radiocarbon was excreted into urine and feces nearly 100% within 7 days. The urinary and fecal excretion accounted for 43-67% and 34-55% of the dose, respectively. Males excreted more radio-activity into feces than females. 14C-Concentration reached a peak in tissues 1 to 8hr after administration. Adrenal and liver showed relatively higher peak concentrations of 4.10-4.57 and 2.34-2.59μg (S)-E equivalents/g tissue decreasing with half-lives of 8-11 and 5-6hr, respectively. 14C-Levels in tissues were generally low on the 7th day after administration. Urinary and fecal metabolites amounting to 83-91% of the dosed 14C were identified, and metabolic pathways for (S)-E were proposed. Recovery of unchanged (S)-E in feces was 7 to 13% of the dose. A main biotransformation was oxidation of the methyl group to form hydroxymethyl and carboxy metabolites, which amounted to 58-75% of the total dose. Slight sex-related differences were observed in amounts of excreted metabolites: females excreted a larger amount of the carboxy metabolite and a smaller amount of 1, 2, 4-triazole into urine than males. Although main metabolic reactions of (S)-E were similar to those of (R)-(E)-1-(2, 4-dichlorophenyl)-4, 4-dimethyl-2-(1, 2, 4-triazol-1-yl)-1-penten-3-ol, diniconazole, there was a difference in the excretion route of the main carboxy metabolites. Rats receiving Tr-14C-(S)-E excreted more 14C into urine than those receiving 14C-diniconazole. It is considered that 14C in the former was excreted into urine more easily than that in the latter because the octanol-water partition coefficient (Po/w) of the carboxy metabolite from (S)-E is smaller than that from diniconazole.
