Physiological disposition and metabolism of O-ethyl-O-4-nitrophenyl phenylphosphonothioate in male cats following a single dermal administration.
The pharmacokinetics and metabolism of a single dermal 20.0 mg/kg of uniformly phenyl-labeled [14C]EPN (O-ethyl O-4-nitrophenyl [14C]phenylphosphonothioate) were investigated in adult male cats. Three treated cats were killed at each time interval: 0.5, 2, 4, 8, and 12. Radioactivity disappeared exponentially from administration site at a rate constant of 0.46 day-1, corresponding to a half-life of 1.5 days. Most of the absorbed radioactivity was excreted in the urine (29.9%). Only 3.2% of the 14C was recovered in the feces. No radioactivity was detected in expired CO2. Only traces of EPN were detected in the urine and feces. Most of the excreted 14C materials were identified as O-ethyl phenylphosphonothioic acid (EPPTA), O-ethyl phenylphosphonic acid (EPPA), and phenylphosphonic acid (PPA). The disposition studies showed that EPN was the major compound identified 0.5 day after administration in the brain, spinal cord, sciatic nerve, adipose tissue, plasma, muscle, liver, and kidney. Most of the radioactivity in the liver and kidney was identified after 4 days as EPPTA, EPPA, and PPA. Kinetic and distribution studies showed that EPN was eliminated from the tissues and plasma according to exponential kinetics. The half-life of the elimination of EPN from plasma was 9.1 days corresponding to a constant rate value of 0.076 day-1. Relative residence (RR) of EPN relative to plasma was longest in the sciatic nerve and shortest in the kidney.
Abou-Donia, MB; Kinnes, CG; Abdo, KM; Bjornsson, TD
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