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Titolo:
Unanticipated plasma concentrations in two clozapine-treated patients
Autore:
Alfaro, CL; McClure, RK; Vertrees, JE; Benavides, R;
Indirizzi:
NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892 H, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA NIMH, Bethesda, MD 20892 USA NIMH Bethesda MD USA 20892NIMH, Bethesda, MD 20892 USA San Antonio State Hosp, Clin Res Unit, San Antonio, TX USA San Antonio State Hosp San Antonio TX USA Res Unit, San Antonio, TX USA Univ Texas, Hlth Sci Ctr, Adv Psychopharmacol Evaluat Lab, San Antonio, TXUSA Univ Texas San Antonio TX USA opharmacol Evaluat Lab, San Antonio, TXUSA
Titolo Testata:
ANNALS OF PHARMACOTHERAPY
fascicolo: 9, volume: 35, anno: 2001,
pagine: 1028 - 1031
SICI:
1060-0280(200109)35:9<1028:UPCITC>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
REFRACTORY SCHIZOPHRENIC-PATIENTS; CLINICAL-RESPONSE; SERUM; NORCLOZAPINE; METABOLITES; MEDICATION; RESISTANT; TIME;
Keywords:
clozapine; cytochrome P450; therapeutic drug monitoring;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Alfaro, CL NIH, Ctr Clin, Dept Pharm, 10 Ctr Dr,Bldg 10,Room 1N257, Bethesda, MD 20892 USA NIH 10 Ctr Dr,Bldg 10,Room 1N257 Bethesda MD USA 20892 0892 USA
Citazione:
C.L. Alfaro et al., "Unanticipated plasma concentrations in two clozapine-treated patients", ANN PHARMAC, 35(9), 2001, pp. 1028-1031

Abstract

OBJECTIVE: To report two cases of lower than anticipated clozapine plasma concentrations despite near maximum recommended doses of clozapine 800-900 mg/d in two medication-compliant schizophrenic inpatients. CASE SUMMARIES: Clozapine therapy was initiated in two male schizophrenic inpatients for treatment of psychotic symptoms refractory to other typical and atypical antipsychotics. Despite receiving adequate doses of clozapine for at least two months, these patients remained symptomatic. Therapeutic drug monitoring was used to target a clozapine plasma concentration of greater than or equal to 250 ng/mL, the minimum value reported in the literatureto be associated with increased clinical response. Clozapine plasma concentrations remained at 200 ng/mL in one patient despite dosage increases from600 to 800 mg/d. In the second patient, administration of the maximum recommended dose resulted in concentrations between 200 and 250 ng/mL. Increasing the clozapine dosage to 1000 mg/d did not increase the clozapine plasma concentration. Evaluation of the ratio of clozapine plasma concentration clozapine to dose yielded lower than expected values compared with those reported in the literature. DISCUSSION: These two patients exhibited lower than anticipated clozapine plasma concentrations despite receiving high doses of clozapine. Several studies evaluating clozapine serum concentrations and clinical response have suggested threshold concentrations of greater than or equal to 350 ng/mL, greater than or equal to 370 ng/mL, or greater than or equal to 420 ng/mL. The only study that randomized patients to three concentration ranges found that patients who achieved a clozapine serum concentration in a medium range (mean 251 ng/mL) responded better than patients in a low range (mean 91 ng/mL) and similar to patients in a high range (mean 396 ng/mL). However, attaining plasma concentrations in this range for these patients proved difficult. Reasons for the low concentrations are unclear and may be related to increased metabolic activity at several cytochrome P450 isoenzymes involvedin the metabolism of clozapine. CONCLUSIONS: These cases illustrate lower than anticipated clozapine plasma concentrations despite high-dose clozapine therapy. Strategies to increase clozapine plasma concentrations in such patients might include adding a drug to partially inhibit the metabolism of clozapine. If those strategies are unacceptable based on risk assessment, patient compliance, or other reasons, clinicians may consider addition of a low-dose typical or other atypical antipsychotic drug to augment clozapine response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/12/19 alle ore 11:18:28