Absorption, Distribution, Metabolism, and Excretion of a New Herbicide, Epyrifenacil, in Rats

The metabolic fate of a newly developed herbicide, epyrifenacil, (ethyl[(3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]phenoxy}pyridin-2-yl)oxy]acetate, S-3100), in rats was determined using C-14-labeled epyrifenacil. When it was administered orally to rats at 1 mg/kg, around 73-74% of the dose was absorbed, metabolized, and mainly excreted into feces within 48 h. The elimination of radioactivity in plasma and tissues was rapid, suggesting that exposure of epyrifenacil and metabolites is small. Metabolite analysis revealed that epyrifenacil was rapidly ester-cleaved to M1 and then mainly excreted into bile or further metabolized. No parent was detected in plasma, tissues, and urine. Remarkably, M1 was mainly distributed in the liver (at a concentration of 70-112 times higher than in plasma at a low dose). Furthermore, a significant sexrelated difference was observed in urinary excretion of M1. Considering the above observations with those in the literature, the organic anion-transporting polypeptide (OATP) likely plays a role on the active transport of M1 in the liver and kidney.

Automated summary

A study examined the metabolic fate of a newly developed herbicide epyrifenacil in rats, finding that it was rapidly metabolized to M1 and mainly excreted through bile. The parent compound was not detected in plasma, tissues, or urine. M1 was predominantly found in the liver, with a significant sex-related difference observed in urinary excretion. The study suggests that organic anion-transporting polypeptide (OATP) may play a role in the active transport of M1 in the liver and kidney.