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Titolo:
Therapeutic drug monitoring of risperidone using a new, rapid HPLC method:Reappraisal of interindividual variability factors
Autore:
Balant-Gorgia, AE; Gex-Fabry, M; Genet, C; Balant, LP;
Indirizzi:
Univitzerlandeva, Dept Psychiat, Therapeut Drug Monitoring Unit, Geneva, Sw Univ Hosp Geneva Geneva Switzerland ut Drug Monitoring Unit, Geneva, Sw Univ Hosp Geneva, Dept Psychiat, Clin Res Unit, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland Clin Res Unit, Geneva, Switzerland
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 1, volume: 21, anno: 1999,
pagine: 105 - 115
SICI:
0163-4356(199902)21:1<105:TDMORU>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; PSYCHOTROPIC MEDICATION; PHARMACOKINETICS; 9-HYDROXYRISPERIDONE; SCHIZOPHRENIA; METABOLISM; NORTRIPTYLINE; IMIPRAMINE; SYMPTOMS; HUMANS;
Keywords:
age effect; analytic method; interindividual variability; risperidone; therapeutic drug monitoring;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Balant-Gorgia, AE Uniteitzerlandng Therapeut, 2 Chemin Petit Bel Air, CH-1225 Chene Bourg, Sw Unite Monitoring Therapeut 2 Chemin Petit Bel Air CheneBourg Switzerland CH-1225
Citazione:
A.E. Balant-Gorgia et al., "Therapeutic drug monitoring of risperidone using a new, rapid HPLC method:Reappraisal of interindividual variability factors", THER DRUG M, 21(1), 1999, pp. 105-115

Abstract

Because of the enormous gap between premarketing studies in physically healthy subjects and clinical practice in patients, the present study reconsidered interindividual variability factors affecting risperidone concentrations under routine therapeutic drug monitoring conditions. The study included92 patients, 27% of whom were 70 years or older. The patients received risperidone orally (dose range, 0.5-11 mg per day) and had concentrations of risperidone and the active metabolite 9-hydroxyrisperidone measured at steady state by a new, rapid, and sensitive method of highperformance liquid chromatography (HPLC). After normalization to a dose of 4 mg/day, median concentrations were 2.9 ng/ml (80% range, 0.9-27.9 ng/ml) for the parent compound and 24.1 ng/ml (80% range, 12.0-57.6 ng/ml) for the metabolite. When considering linear regression models, age was identified as a major source of interindividual variability, with expected increases of 340% and 220% for concentrations of parent compound and metabolite, with age increasing from 20to 80 years. Body weight provided an additional significant contribution to the variability of 9-hydroxyrisperidone concentration, a 20-kg higher body weight associated with a concentration decrease of 23%. Serotonin-specific reuptake inhibitor (SSRI) comedication (fluoxetine, two patients; citalopram; two patients; paroxetine, one patient; fluvoxamine, one patient) was significantly associated with 4.6-fold higher concentrations of parent compound, in keeping with an inhibitory action on CYP2D6 enzyme. Significantly higher concentrations of 9-hydroxy-risperidone (+29%) were also observed in the 17 patients with biperiden comedication. Therapeutic drug monitoring data, collected in patients representative of the population for which the drug was intended, allowed us to quantify the dose reduction needed in elderly patients and thus provided valuable information in addition to the one collected during premarketing studies performed with strict inclusion and exclusion criteria.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:41:43