Phencyclidine (PCP) disposition kinetics in dogs as a function of dose and route of administration

J. R. Woodworth, S. M. Owens, Michael Mayersohn

Research output: Contribution to journalArticle

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Abstract

Phencyclidine (PCP) disposition kinetics has been examined in dogs as a function of dose and after i.v. and p.o. administration. Intravenous doses ranged from a tracer quantity of [3H]PCP to 5 mg/kg of unlabeled PCP. The elimination half-life of intact PCP was relatively short with harmonic mean values of 2.7, 5.4 and 3.9 hr for the tracer, 1- and 5-mg/kg doses, respectively. In contrast, measurement of total radioactivity gave a much longer half-life (35-52 hr) suggesting slower metabolite elimination. The drug has a large apparent volume of distribution (weighted mean of 20 liters/kg) and a systemic clearance (which is primarily metabolic) that approaches estimates of liver blood flow in the dog. Renal clearance of intact PCP represents a small fraction of total clearance. Percentage of the [3H]PCP dose recovered as total radioactivity was 49% in urine and 12% in feces. Several metabolites of PCP were determined in urine and they account for about 30% of the dose with the aminopentanoic acid derivative being present in the greatest amount. One of the hydroxylated metabolites is present in cis- and trans-forms, with the latter predominating. Three animals received an i.v. dose of [3H]PCP and a p.o. dose of unlabeled PCP at the same time to determine absolute bioavailability. Approximately 25% of the dose is absorbed intact. The p.o. (intrinsic) clearance of PCP is about four times greater than systemic clearance suggesting a blood flow-dependence in clearance and substantial first-pass hepatic metabolism.

Original languageEnglish (US)
Pages (from-to)654-661
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume234
Issue number3
StatePublished - 1985

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Phencyclidine
Radioactivity
Half-Life
Urine
Dogs
Liver
Feces
Biological Availability
Kidney
Acids
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Phencyclidine (PCP) disposition kinetics in dogs as a function of dose and route of administration. / Woodworth, J. R.; Owens, S. M.; Mayersohn, Michael.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 234, No. 3, 1985, p. 654-661.

Research output: Contribution to journalArticle

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abstract = "Phencyclidine (PCP) disposition kinetics has been examined in dogs as a function of dose and after i.v. and p.o. administration. Intravenous doses ranged from a tracer quantity of [3H]PCP to 5 mg/kg of unlabeled PCP. The elimination half-life of intact PCP was relatively short with harmonic mean values of 2.7, 5.4 and 3.9 hr for the tracer, 1- and 5-mg/kg doses, respectively. In contrast, measurement of total radioactivity gave a much longer half-life (35-52 hr) suggesting slower metabolite elimination. The drug has a large apparent volume of distribution (weighted mean of 20 liters/kg) and a systemic clearance (which is primarily metabolic) that approaches estimates of liver blood flow in the dog. Renal clearance of intact PCP represents a small fraction of total clearance. Percentage of the [3H]PCP dose recovered as total radioactivity was 49{\%} in urine and 12{\%} in feces. Several metabolites of PCP were determined in urine and they account for about 30{\%} of the dose with the aminopentanoic acid derivative being present in the greatest amount. One of the hydroxylated metabolites is present in cis- and trans-forms, with the latter predominating. Three animals received an i.v. dose of [3H]PCP and a p.o. dose of unlabeled PCP at the same time to determine absolute bioavailability. Approximately 25{\%} of the dose is absorbed intact. The p.o. (intrinsic) clearance of PCP is about four times greater than systemic clearance suggesting a blood flow-dependence in clearance and substantial first-pass hepatic metabolism.",
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