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Titolo:
WILL ROUTINE THERAPEUTIC DRUG-MONITORING HAVE A PLACE IN CLOZAPINE THERAPY
Autore:
FREEMAN DJ; OYEWUMI LK;
Indirizzi:
JOHN P ROBARTS RES INST,DIV CLIN PHARMACOL,100 PERTH DR LONDON ON N6A5K8 CANADA UNIV WESTERN ONTARIO,DEPT MED LONDON ON CANADA UNIV WESTERN ONTARIO,DEPT PSYCHIAT LONDON ON N6A 3K7 CANADA
Titolo Testata:
Clinical pharmacokinetics
fascicolo: 2, volume: 32, anno: 1997,
pagine: 93 - 100
SICI:
0312-5963(1997)32:2<93:WRTDHA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; REFRACTORY SCHIZOPHRENIC-PATIENTS; MULTIPLE-DOSE PHARMACOKINETICS; PLASMA CLOZAPINE; CLINICAL-RESPONSE; SERUM CONCENTRATIONS; INDUCED AGRANULOCYTOSIS; ULTRAVIOLET DETECTION; DESMETHYLCLOZAPINE; NORCLOZAPINE;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
D.J. Freeman e L.K. Oyewumi, "WILL ROUTINE THERAPEUTIC DRUG-MONITORING HAVE A PLACE IN CLOZAPINE THERAPY", Clinical pharmacokinetics, 32(2), 1997, pp. 93-100

Abstract

Clozapine is an atypical antipsychotic medication with proven efficacy in the management of refractory schizophrenia. It is also recommended for patients who do not tolerate the extrapyramidal adverse effects of traditional antipsychotic medications. However, the therapeutic promise of clozapine has been limited by a higher incidence of agranulocytosis. Currently, plasma clozapine concentrations are not routinely used in clinical management. Therapeutic effects are monitored empirically during a 6 to 8 week titration period in which the dosage is raisedto 300 to 450 mg/day. Clozapine nevertheless fulfils a number of criteria which make it a candidate for therapeutic monitoring. These include an identifiable therapeutic range, an unpredictable dose-concentration relationship between patients, a potential for clinically relevantpharmacokinetic interaction with other drugs and a high probability of patient noncompliance. The therapeutic threshold plasma concentration appears to be about 400 mu g/L. Concentrations above 1000 mu g/L increase the risk of adverse effects on the central nervous system (confusion, delirium and generalised seizures). There is no evidence to linkincreased concentrations of clozapine or its metabolite to the development of agranulocytosis. We conclude that therapeutic drug monitoringcan play a useful role in the clinical management of patients treatedwith clozapine. The clinician is advised to primarily use clinical judgement during dosage escalation, but intermittent monitoring is recommended to quickly optimise a therapeutic dosage for each patient. At steady state, occasional measurements could be made when clinical signsindicate possible toxicity or lack of effect (possibly caused by a lack of compliance or drug interaction). Long term monitoring would, in our view, not be necessary.

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Documento generato il 21/01/20 alle ore 01:22:26