Metabolism of methyl-(E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate (azoxystrobin) in rat.
1. The metabolic fate of [(14)C]-methyl-(E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate (azoxystrobin) was determined in the male and female rat following a single oral dose of 1 and 100 mg x kg(-1) and in surgically prepared, bile duct-cannulated rats following a single oral dose of 100 mg x kg(-1). 2. Azoxystrobin was extensively metabolized with at least 15 metabolites. There was a sex difference, with females producing more metabolites than males. 3. The two principal metabolic pathways were hydrolysis of the methoxyacid followed by glucuronic acid conjugation and glutathione conjugation of the cyanophenyl ring followed by further metabolism leading to the mercapturic acid. There were also several other minor pathways.
Laird
W J D
WJ
Syngenta Central Toxicology Laboratory, Alderley Park SK10 4TJ, UK. william.laird@syngenta.com
Gledhill
A J
AJ
Lappin
G J
GJ
D000179:Acrylates / Q000493:pharmacokinetics*; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D003640:Dealkylation; D005243:Feces / Q000737:chemistry; D005260:Female; D005659:Fungicides, Industrial / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000378:metabolism; D006900:Hydroxylation; D007536:Isomerism; D008297:Male; D008689:Methacrylates; D011743:Pyrimidines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D021241:Spectrometry, Mass, Electrospray Ionization; D000073739:Strobilurins
D000179:Acrylates; D005659:Fungicides, Industrial; D020719:Glucuronides; D008689:Methacrylates; D011743:Pyrimidines; D000073739:Strobilurins; D003545:Cysteine; C087670:azoxystrobin