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Titolo:
Cocaine pharmacodynamics after intravenous and oral administration in rats: relation to pharmacokinetics
Autore:
Ma, F; Falk, JL; Lau, CE;
Indirizzi:
Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 chol, Piscataway, NJ 08854 USA
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 4, volume: 144, anno: 1999,
pagine: 323 - 332
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; DISCRIMINATIVE MOTOR FUNCTIONS; RELATING DRL PERFORMANCE; PLASMA-CONCENTRATIONS; DIFFERENTIAL REINFORCEMENT; INDEPENDENT INTERACTION; SERUM MICROSAMPLES; ALPRAZOLAM; CAFFEINE; HUMANS;
Keywords:
absolute oral bioavailability; cocaine; benzoylecgonine; norcocaine; pharmacokinetics; pharmacodynamics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Lau, CE Rutgers State Univ, Dept Psychol, 152 Freulinghuysen Rd, Piscataway, NJ 08854 USA Rutgers State Univ 152 Freulinghuysen Rd Piscataway NJ USA 08854 A
Citazione:
F. Ma et al., "Cocaine pharmacodynamics after intravenous and oral administration in rats: relation to pharmacokinetics", PSYCHOPHAR, 144(4), 1999, pp. 323-332

Abstract

Rationale: To design optimal dose regimes for oral cocaine, it is essential to characterize pharmacokinetics (PK) of cocaine after IV and PO administration. Objectives: To investigate the absolute bioavailability of oral cocaine, its effectiveness and the relation between PK and PD in a within-subject design. Methods: We used the effects of IV and PO cocaine on a contingency-controlled timing behavior, the differential reinforcement of low rate schedule (DRL 45-s) in 3-h sessions, as the PD measures [i.e., the shorter-response rate (srr) and the reinforcement rate (rr)]. Cocaine PK parameterswere determined by simultaneous modeling of the concentration-time profiles (CTPs) after IV 2 mg/kg and PO 20 mg/kg cocaine administration. The absolute oral cocaine bioavailability was determined pharmacokinetically (F) andpharmacodynamically (F-srr and F-rr). Results: IV and PO cocaine increasedthe shorter response rate and decreased the reinforcement rate in a dose- and time-related fashion, which mirrored the respective prototypical serum cocaine CTPs. After the absorption phase, the serum cocaine CTP of PO cocaine paralleled that of IV cocaine. The duration of action for PO cocaine waslonger than that for IV cocaine owing to its larger mean residence time. The active metabolite, norcocaine, was not detected after IV but after PO cocaine administration. The value of F was 4.66% which was significantly lower than the values of F-srr (13.67%) and F-rr (32.63%). Furthermore, the concentration-effect relations for the reinforcement rate revealed that PO cocaine was more potent than IV cocaine. Conclusions: Oral cocaine is more effective behaviorally than from predictions made in terms of its PK. The differences in active metabolite profiles as well as the rate and extent of acute tolerance for IV versus PO cocaine may account for the greater potency observed for oral cocaine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:29:58