Add time:09/30/2019         Source:sciencedirect.com

Fluphenazine-14C, 4-[1-14C-3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazineethanol dihydrochloride, was administered orally to dogs at 10 and 40 mg./kg. and to monkeys at 10 mg./kg. After an oral dose of 10 mg./kg., dogs excreted 2-4% and 75-89% of the dose in the urine and feces, respectively. Monkeys that received 10 mg./kg. orally excreted 12-19% and 56-69% of the dose in the urine and feces, respectively. After an oral dose of 40 mg./kg., dogs excreted 5-18% and 85-110% of the dose in the urine and feces, respectively. After 10 mg./kg. i.v., a dog excreted 1.2, 62.0, and 0.03% of the dose in the urine, bile, and expired air, respectively, in 7 hr. After an oral dose of 40 mg./kg., dogs had the highest concentrations of radioactivity in the liver; lungs; combined retina, choroid, and sclera; and kidneys. Localization of radioactivity to gross areas of the brain was not demonstrable. In addition to fluphenazine sulfoxide, several metabolites were present in the urine of dogs and monkeys. In the feces, in addition to fluphenazine-14C, one major and two minor metabolites were found in both species. As the oral dose of fluphenazine-14C administered to dogs was increased from 10 to 40 mg./kg., the amount of unchanged fluphenazine-14C increased relative to the major metabolite. The major metabolite was unconjugated in the feces but was present as the glucuronide conjugate in the bile.

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