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Titolo:
Population pharmacokinetics of clomipramine, desmethylclomipramine, and hydroxylated metabolites in patients with depression receiving chronic treatment: Model evaluation
Autore:
Gex-Fabry, M; Haffen, E; Paintaud, G; Bizouard, P; Sechter, D; Bechtel, PR; Balant, LP;
Indirizzi:
Univ Hosp Geneva, Dept Psychiat, Clin Res Unit, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland Clin Res Unit, Geneva, Switzerland Besancon Univ Hosp, Dept Psychiat, Besancon, France Besancon Univ Hosp Besancon France osp, Dept Psychiat, Besancon, France Tours Univ Hosp, Dept Pharmacol, Tours, France Tours Univ Hosp Tours France s Univ Hosp, Dept Pharmacol, Tours, France Univ Besancon, Fac Med, F-25030 Besancon, France Univ Besancon Besancon France F-25030 Fac Med, F-25030 Besancon, France
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 6, volume: 22, anno: 2000,
pagine: 701 - 711
SICI:
0163-4356(200012)22:6<701:PPOCDA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLINICAL-RESPONSE; PLASMA; IMIPRAMINE; NORTRIPTYLINE; SPARTEINE; KINETICS; CYP2D6;
Keywords:
pharmacokinetics; population; clomipramine; metabolites;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Gex-Fabry, M Dept Psychiat, Clin Res Unit, 2 Chemin Petit Bel Air, CH-1225Chene Bourg,Switzerland Dept Psychiat 2 Chemin Petit Bel Air Chene Bourg Switzerland CH-1225
Citazione:
M. Gex-Fabry et al., "Population pharmacokinetics of clomipramine, desmethylclomipramine, and hydroxylated metabolites in patients with depression receiving chronic treatment: Model evaluation", THER DRUG M, 22(6), 2000, pp. 701-711

Abstract

Because metabolites play a major role in the clinical response to clomipramine, the objective of the current study was to develop a population model and evaluate its performance to describe the pharmacokinetic profiles of clomipramine (C) and its active metabolites desmethylclomipramine (DC), 8-hydroxy-clomipramine (OHC) and 8-hydroxy-desmethylclomipramine (OHDC). A firstsample of 14 patients served for development of a 2-molecule C and DC model, which was shown to provide reasonable estimates of AUG-based clearances,as well as precise estimation of interindividual variability. Simulated data, generated to mimic a semi-rich sampling design and chronic treatment with clomipramine, indicated that clearance estimation was feasible under routine treatment conditions. A second sample of 30 patients, recruited prospectively and followed for a median 4-week period, was used to extend the 2-molecule model to a 4-molecule model. Goodness-of-fit assessment revealed that model-predicted concentrations were reasonably close to observed concentrations for a majority of patients. Interindividual variability was 50% to 60% for hydroxylation and desmethylation clearances, and residual variability was 30%. The proposed model incorporates much of what is known about themetabolism of clomipramine and may valuably integrate the influence of genetic and environmental factors on each metabolic pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 10:44:46