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Titolo:
Olanzapine: Pharmacology, pharmacokinetics and therapeutic drug monitoring
Autore:
Rao, ML; Hiemke, C; Grasmader, K; Baumann, P;
Indirizzi:
Univ Bonn, Klin & Poliklin Psychiat & Psychotherapie, D-5300 Bonn, GermanyUniv Bonn Bonn Germany D-5300 iat & Psychotherapie, D-5300 Bonn, Germany Univ Mainz, Psychiat Klin, D-6500 Mainz, Germany Univ Mainz Mainz Germany D-6500 nz, Psychiat Klin, D-6500 Mainz, Germany Univ Prilly, Dept Psychiat Adulte, Unite Biochim & Psychopharmacol Clin, Prilly, Switzerland Univ Prilly Prilly Switzerland sychopharmacol Clin, Prilly, Switzerland
Titolo Testata:
FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE
fascicolo: 11, volume: 69, anno: 2001,
pagine: 510 - 517
SICI:
0720-4299(200111)69:11<510:OPPATD>2.0.ZU;2-O
Fonte:
ISI
Lingua:
GER
Soggetto:
ANTIPSYCHOTIC AGENT OLANZAPINE; PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA-LEVELS; ELECTROCHEMICAL DETECTION; INDUCED AGRANULOCYTOSIS; SERUM CONCENTRATIONS; RECEPTOR OCCUPANCY; SCHIZOPHRENIA; HALOPERIDOL; CLOZAPINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Rao, ML Klin & Poliklin Psychiat, Sigmund Freud Str 25, D-53105 Bonn, Germany Klin & Poliklin Psychiat Sigmund Freud Str 25 Bonn Germany D-53105
Citazione:
M.L. Rao et al., "Olanzapine: Pharmacology, pharmacokinetics and therapeutic drug monitoring", F NEUR PSYC, 69(11), 2001, pp. 510-517

Abstract

Olanzapine is an effective and safe antipsychotic drug. Its pharmacokinetic properties are comparable to those of classical antipsychotics. Oxidativeprocesses are mediated by the cytochrome P450 isoenzyme CYP1A2 and to a minor degree by CYP2D6. Olanzapine's main route of metabolism is by glucuronidation. Therapeutic doses result in a wide variability of serum levels; dose and serum concentration are linearly correlated. Smoking and carbamazepine induce cytochrome P450 isoenzymes and thus decrease olanzapine serum levels. Inhibition of CYP1A2 by fluvoxamine yields increased concentrations; however, clinically relevant CYP2D6 inhibition was observed only in combination with additional disposition factors, such as female gender or old age. As a rule dose adjustment is not necessary but moderate renal or hepatic impairment calls for control of serum levels to provide maximal safety during olanzapine therapy. Therapeutic drug monitoring (TDM) and toxicology studies are carried out by HPLC methods using UV or MS detection. The optimal therapeutic range of olanzapine serum levels is 20 to 40 ng/ml. Concentrationsof 80 ng/ml are considered threshold for the occurrence of adverse events;however, toxicological studies showed that postmortem plasma levels are higher than antemortem levels. Lethality of high olanzapine was only observedin combination with other drugs. Moderate increases of prolactin levels were detected during administration of olanzapine. In relation to olanzapine therapy, several case reports of neutropenia and agranulocytosis appeared in the literature. Weight gain in olanzapine-treated patients does not correlate with serum levels. Ol-anzapine response is augmented when patients' serum levels are titrated to 20 to 40 ng/ml thereby minimizing the occurrenceof side effects, thus TDM is recommended for patients treated with olanzapine.

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Documento generato il 19/01/20 alle ore 06:18:07