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Titolo:
Intravenous and oral clozapine pharmacokinetics, pharmacodynamics, and concentration-effect relations: acute tolerance
Autore:
Sun, L; Lau, CE;
Indirizzi:
Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 chol, Piscataway, NJ 08854 USA Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 Chem, Piscataway, NJ 08854 USA
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 398, anno: 2000,
pagine: 225 - 238
SICI:
0014-2999(20000616)398:2<225:IAOCPP>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
TIMING PERFORMANCE DEFICITS; RELATING DRL PERFORMANCE; DIFFERENTIAL-REINFORCEMENT; N-DESMETHYLCLOZAPINE; BLOOD-CONCENTRATIONS; SQUIRREL-MONKEYS; RATS; HALOPERIDOL; ALPRAZOLAM; MIDAZOLAM;
Keywords:
acute tolerance; clozapine, intravenous; clozapine, oral; pharmacodynamics; pharmacokinetics; pharmacokinetic-pharmacodynamic modeling; potency, relative;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Lau, CE Rutgers State Univ, Dept Psychol, 152 Frelinghuysen Rd, Piscataway, NJ 08854 USA Rutgers State Univ 152 Frelinghuysen Rd Piscataway NJ USA 08854 SA
Citazione:
L. Sun e C.E. Lau, "Intravenous and oral clozapine pharmacokinetics, pharmacodynamics, and concentration-effect relations: acute tolerance", EUR J PHARM, 398(2), 2000, pp. 225-238

Abstract

We examined the pharmacokinetics and pharmacodynamics of intravenous (1-5 mg/kg) and oral clozapine (2.5-10 mg/kg) in rats (terminal half-life = 81.8min; oral bioavailability = 5.32%). Both dose- and concentration-effect relations of clozapine were characterized. Clozapine's effects were similar to those of benzodiazepines because of the similarity in effect-time profiles between the two classes of drugs. The IC50 value increased as a function of dose; consequently, clozapine's relative potency decreased linearly withthe logarithm of AUC((0-infinity)), or bioavailable dose regardless of route of administration. The IC50 is an index for the sensitivity of behavioral performance to clozapine; relative potency provides an index for estimating the extent of acute tolerance. As IC50 increases, relative potency decreases, and consequently, acute tolerance increases. Our results demonstratedthat greater acute tolerance was observed for i.v. clozapine than for p.o.clozapine; however, clozapine exhibited a single concentration-effect relation across dose and route of administration after correcting for relative potencies. (C) 2000 Elsevier Science B.V. All rights reserved.

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Documento generato il 27/02/20 alle ore 16:26:20