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Titolo:
In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine
Autore:
Chang, WH; Augustin, B; Lane, HY; ZumBrunnen, T; Liu, HC; Kazmi, Y; Jann, MW;
Indirizzi:
Taipei City Psychiat Ctr, Lab Biol Psychiat, Taipei, Taiwan Taipei City Psychiat Ctr Taipei Taiwan ab Biol Psychiat, Taipei, Taiwan Mercer Univ, So Sch Pharm, Atlanta, GA USA Mercer Univ Atlanta GA USAMercer Univ, So Sch Pharm, Atlanta, GA USA Hung Chi Psychiat Hosp, Taipei, Taiwan Hung Chi Psychiat Hosp Taipei Taiwan Chi Psychiat Hosp, Taipei, Taiwan
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 1, volume: 145, anno: 1999,
pagine: 91 - 98
Fonte:
ISI
Lingua:
ENG
Soggetto:
REFRACTORY SCHIZOPHRENIC-PATIENTS; SEROTONIN REUPTAKE INHIBITORS; PHARMACOKINETIC INTERACTIONS; CLINICAL-RESPONSE; SERUM LEVELS; METABOLISM; DISPOSITION; DESMETHYLCLOZAPINE; NORCLOZAPINE; ERYTHROMYCIN;
Keywords:
clozapine; fluvoxamine; CYP 450; drug-drug interaction; in-vitro; in-vivo;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Chang, WH Taipei City Psychiat Ctr, Lab Biol Psychiat, 309 Sung Te Rd, Taipei, Taiwan Taipei City Psychiat Ctr 309 Sung Te Rd Taipei Taiwan , Taiwan
Citazione:
W.H. Chang et al., "In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine", PSYCHOPHAR, 145(1), 1999, pp. 91-98

Abstract

The drug-drug interaction between fluvoxamine (FLV) and clozapine (CLZ) was evaluated by in-vitro and in-vivo methods. In-vitro studies were conducted using human hepatic microsomal preparations with standard chemical inhibitors of the cytochrome P450 (CYP 450) isozyme system. Furafyline, FLV, troleandomycin (TAO) and erythromycin were used as the chemical inhibitors. Forthe in-vivo study, nine male schizophrenic patients were administered a single dose of CLZ 50 mg on two separate occasions with a 2-week FLV treatment of 50 mg twice a day in between each CLZ dose. Blood samples were obtained over 48 h following CLZ administration. CLZ and its two principle metabolites, clozapine N-oxide (CNO) and desmethylclozapine (DCLZ), were measured by high performance liquid chromatography with ultraviolet detection for both in-vitro and in-vivo studies. The in-vitro formation of DCLZ was inhibited by furafyline and FLV by 42.0% and 48.5% (P < 0.01), respectively. TAO and erythromycin had only modest inhibition effects on DCLZ formation of 18.3% and 21.0% (P = NS), respectively. CNO in-vitro formation was significantly reduced by TAO and erythromycin by 44.5% and 45.0% (P < 0.01), respectively. Furafyline and FLV had only modest effects of 19.2% and 8.5% (P = NS),respectively. In schizophrenic patients, FLV resulted in a pronounced increased in CLZ plasma concentrations with the total mean CLZ AUC increased bya factor of 2.58 from 780.8 ng/ml per hour to 2218.0 ng/ml per hour (P < 0.001). All patients were sedated during combined FLV and CLZ use. During FLV treatment, CNO and DCLZ AUC both decreased by 18.8% (P = 0.07) and 9.0% (P = NS), respectively. These results indicate that in-vitro evaluations maynot always accurately reflect changes in drug-drug interaction observed in-vivo. Careful patient monitoring is recommended during FLV/CLZ co-administration.

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Documento generato il 25/01/20 alle ore 19:13:58