Pharmacokinetic and pharmacodynamic evaluation of phencyclidine and its decadeutero variant
The role of metabolism in the in vivo actions of phencyclidine (PCP) was examined by comparing deuterium-substituted drug with drug of normal isotopic abundance. PCP elicits two responses that differ in their time course, ataxia, which is observable immediately after dosage, and hypothermia, which peaks approximately 90 to 120 min after drug administration. The role of metabolism in these responses was determined by comparing bioavailabilities of deuterium enriched (d10) and normal (d0) PCP with the two responses. Plasma concentration was determined after the i.v. and i.p. administration of d10 and d0 drug and the bioavailability of the d10 was found to be 1.3 to 1.5 times the d0. The clearance of the d10 was also smaller than the d0. The d10, which is pharmacologically equivalent in vitro, is metabolized more slowly than the d0 in vitro. The pharmacokinetic and pharmacodynamic bioavailabilities exhibited comparable isotope effects, indicating that both responses are due to the actions of the parent drug.
- Research Organization:
- Univ. of California, Los Angeles (USA)
- OSTI ID:
- 5822123
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 250:1
- Country of Publication:
- United States
- Language:
- English
Similar Records
Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action
Pharmacokinetics of buspirone as determined by ex vivo (/sup 3/H)-DPAT binding
Related Subjects
PIPERIDINES
METABOLISM
BEHAVIOR
BIOCHEMICAL REACTION KINETICS
BRAIN
DEUTERIUM
ISOTOPE EFFECTS
LIVER
MICROSOMES
RATS
TRACER TECHNIQUES
AMINES
ANIMALS
AZINES
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PYRIDINES
REACTION KINETICS
RIBOSOMES
RODENTS
STABLE ISOTOPES
VERTEBRATES
550501* - Metabolism- Tracer Techniques