PMID: 3746667Sep 1, 1986Paper

Disposition kinetics of the monohydroxy metabolites of phencyclidine in the dog

The Journal of Pharmacology and Experimental Therapeutics
J R WoodworthS M Owens

Abstract

The monohydroxy metabolites of phencyclidine (PCP) have been suggested to contribute to the pharmacologic activity of PCP, and perhaps account for its prolonged action. The disposition kinetics of the monohydroxy metabolites of PCP were examined in dogs. Intravenous doses of the piperidine-hydroxylated metabolite (PCHP) and the trans- and cis-forms of the cyclohexyl-hydroxylated metabolite (trans-PPC and cis-PPC) were each administered to three dogs. The elimination half-life of each metabolite was short, with harmonic mean values of 1.29, 0.98 and 0.92 hr for PCHP, trans-PPC and cis-PPC, respectively. The compounds had large volumes of distribution, with average values of 6.7, 4.7 and 4.4 liters/kg for PCHP, trans-PPC and cis-PPC, respectively. Systemic clearances were high for each compound (51.9, 50.9 and 54.2 ml/min/kg for PCHP, trans-PPC and cis-PPC, respectively), but renal clearances were low (average values ranged from 2 to 8% of systemic clearance), suggesting that these metabolites undergo further metabolism. Analysis of acid-hydrolyzed serum and urine samples indicated that all three compounds were conjugated and that these conjugates were the primary metabolites. The conjugated metabolites exhibited elimination half...Continue Reading

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