Abstract
Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] was examined in male and female SD rats. After single oral administration of [dichlorophenyl-14C]pyridalyl at 5 or 500 mg/kg, the 14C-concentration in blood reached maxima at 2-10 hours and then decreased rapidly with a biological half-life of about 11 - 12 hours. 14C-Concentrations in liver, fat, adrenal and spleen were relatively high at low dose, reaching 2.3 - 2.7 ppm, 1.9 - 2.3 ppm, 1.1 - 1.9 ppm and 1.4 ppm, respectively in these tissues at 2 to 24 hours after administration. Though 14C-elimination from fat and hair & skin were relatively slow as compared to other tissues, the total residue on the 7th day was low, in the range of 1.3 - 2.3% of the dose. The 14C-distribution in tissues with high dose, as examined by whole-body autoradiography, was similar to that observed for the low dose. Results revealed that over 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 - 2.6% and 98.7 - 101.4%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and MS spectrometry. Residual 14C in fat was extracted and analysis by TLC chromatography showed it to be due to pyridalyl itself. No marked sex-related differences were observed in 14C-elimination, 14C-distribution and metabolites.
Footnotes
- Received June 9, 2009.
- Accepted September 16, 2009.
- The American Society for Pharmacology and Experimental Therapeutics