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.
Cho
A K
AK
Department of Pharmacology, University of California, Los Angeles School of Medicine.
Hiramatsu
M
M
Pechnick
R N
RN
Di Stefano
E
E
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*
D003903:Deuterium; D010622:Phencyclidine