Metabolism of furametpyr. 2. (14)C excretion, (14)C concentrations in tissues, and amounts of metabolites in rats.
14C-Labeled furametpyr [N-(1,3-dihydro-1,1, 3-trimethylisobenzofuran-4-yl)-5-chloro-1, 3-dimethylpyrazole-4-carboxamide, Limber] was dosed to male and female rats at 1 (low dose) and 200 or 300 mg/kg (high dose). Elimination of furametpyr was rapid, and the dosed (14)C was substantially excreted within 7 days (45.5-53.3% in feces, 44.1-53. 8% in urine, and 0.01% in expired air). However, (14)C excretion rate showed sex- and dose-related differences, more rapid in males at low dose. (14)C concentrations in tissues decreased rapidly to generally low levels at 7 days (<0.004 ppm with the low dose and <1. 1 ppm with the high dose). Forty metabolites were detected, and 13 metabolites and 4 glucuronides were identified. A small amount of unchanged furametpyr was detected in feces (0.1-0.5% of the dose). The major metabolites in tissues were N-demethylated metabolites. In a bile study, 52.5-54.2% of the dosed (14)C was rapidly excreted into bile within 2 days. The absorption ratio was estimated to be >93.7% for the low dose (1 mg/kg). Major metabolites in bile were glucuronic acid conjugates of furametpyr hydroxides. On the basis of the results, furametpyr is substantially absorbed from the gastrointestinal tract after oral administration, rapidly distributed to tissues, extensively metabolized, and excreted into urine and bile or feces.
Nagahori
H
H
Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-0022, Japan. nagahori@sc.sumitomo-chem.co.jp
Yoshino
H
H
Tomigahara
Y
Y
Isobe
N
N
Kaneko
H
H
Nakatsuka
I
I
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005260:Female; D005659:Fungicides, Industrial / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011720:Pyrazoles / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D014018:Tissue Distribution
D001572:Benzofurans; D002250:Carbon Radioisotopes; D005659:Fungicides, Industrial; D011720:Pyrazoles; C417978:furametpyr