PT  - JOURNAL ARTICLE
AU  - Hirohisa Nagahori
AU  - Koichi Saito
AU  - Yoshitaka Tomigahara
AU  - Naohiko Isobe
AU  - Hideo Kaneko
TI  - Metabolism of Pyridalyl in Rats
AID  - 10.1124/dmd.109.028878
DP  - 2009 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 2284--2289
VI  - 37
IP  - 12
4099  - http://dmd.aspetjournals.org/content/37/12/2284.short
4100  - http://dmd.aspetjournals.org/content/37/12/2284.full
SO  - Drug Metab Dispos2009 Dec 01; 37
AB  - Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] was examined in male and female Sprague-Dawley rats. After a single oral administration of [dichlorophenyl-14C]pyridalyl at 5 or 500 mg/kg, the 14C concentration in blood reached maxima at 2 to 10 h and then decreased rapidly with a biological half-life of approximately 11 to 12 h. 14C concentrations in liver, fat, adrenal gland, and spleen were relatively high at a low dose, reaching 2.3 to 2.7, 1.9 to 2.3, 1.1 to 1.9, and 1.4 ppm, respectively, in these tissues at 2 to 24 h after administration. Although 14C elimination from fat and hair and skin was relatively slow compared with that from other tissues, the total residue on the 7th day was low, in the range of 1.3 to 2.3% of the dose. The 14C distribution in tissues with a high dose, as examined by whole-body autoradiography, was similar to that observed for the low dose. Results revealed that more than 88% of the dosed radiocarbon was excreted within 1 day after administration, with cumulative 14C excretion into urine and feces 7 days after administration of 1.7 to 2.6 and 98.7 to 101.7%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and mass spectrometry. Residual 14C in fat was extracted, and analysis by thin-layer chromatography showed it to be due to pyridalyl itself. No marked sex-related differences were observed in 14C elimination, 14C distribution, and metabolites.Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics