Pharmacokinetics and metabolism of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in Fischer 344 rats

Abstract

Triclopyr, (3,5,6-trichloro-2-pyridinyloxyacetic acid) is the active component of GARLON (trademark of the Dow Chemical Company) brand herbicide. [ 14C]Triclopyr was administered orally to groups of 5 rats/sex as a single 3 and 60 mg/kg body weight dose and as a multiple 3 mg/kg nonradiolabeled dose for 14 days followed by a single 3 mg [ 14C]triclopyr/kg dose on day 15. A fourth group (5 rats/sex) was administered a single 3 mg/kg intravenous dose of [ 14C]triclpyr. In addition, two groups of male rats (3/dose) were used to obtain 14C plasma time-course data and were orally administered [ 14C]triclopyr at doses of 3 and 60 mg/kg. Between 94 and 97% of the administered radioactivity was recovered, and the principal route of excretion was the urine (89–95%). The feces contained <3% of the dose and the expired 14CO 2 and cage wash accounted for less than 0.2 and 1% of the dose, respectively. The tissues and carcass accounted for <2% of the radioactivity at 72 h post-dosing. [ 14C]Triclopyr was rapidly and completely absorbed after oral administration of 3 and 60 mg/kg. The radioactivity was cleared from the plasma of male rats at 3 mg/kg in a mono-exponential manner, with an apparent first-order elimination half-life of 3.6 h. The primary difference between the 3 and 60 mg/kg dose kinetics was the saturation of renal elimination of triclopyr through 9 h post-dosing for the 60 mg/kg group. [ 14C]Triclopyr was primarily excreted unchanged in the urine (81 –96% of the urinary radioactivity), although 4 minor urinary metabolites were noted. Aside from the initial saturation of renal elimination of triclopyr at 60 mg/kg, there were no appreciable differences in the absorption, disposition, or metabolism of [ 14C]triclopyr, based on sex, or prior exposure.