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Titolo:
TISSUE CONCENTRATIONS OF CLOZAPINE AND ITS METABOLITES IN THE RAT
Autore:
BALDESSARINI RJ; CENTORRINO F; FLOOD JG; VOLPICELLI SA; HUSTONLYONS D; COHEN BM;
Indirizzi:
MCLEAN HOSP,MAILMAN RES CTR,115 MILL ST BELMONT MA 02178 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT BOSTON MA 02115 HARVARD UNIV,SCH MED,NEUROSCI PROGRAM BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT PATHOL BOSTON MA 02115 MASSACHUSETTS GEN HOSP,CLIN CHEM LAB BOSTON MA 02114
Titolo Testata:
Neuropsychopharmacology
fascicolo: 2, volume: 9, anno: 1993,
pagine: 117 - 124
SICI:
0893-133X(1993)9:2<117:TCOCAI>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMA-LEVELS; BRAIN; FLUOXETINE;
Keywords:
CLOZAPINE; CLOZAPINE-N-OXIDE; DRUG ASSAY; FLUOXETINE; LIQUID CHROMATOGRAPHY; NORCLOZAPINE; PHOTODIODE-ARRAY; SPECTROPHOTOMETRY; VALPROIC ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
R.J. Baldessarini et al., "TISSUE CONCENTRATIONS OF CLOZAPINE AND ITS METABOLITES IN THE RAT", Neuropsychopharmacology, 9(2), 1993, pp. 117-124

Abstract

Clozapine (CLZ) and its metabolites norclozapine (NOR) and clozapine-N-oxide (NOX) were assayed in rat serum and brain tissue after intraperitoneal injection of CLZ. Clozapine levels rose with dose, averaging 28 ng/ml (87 nmol/L) serum per milligram/kilogram dose. Brain- and serum-CLZ levels correlated closely, averaging 24-fold higher in brain. Norclozapine and NOX averaged approximately 58% and 13% of CLZ in serum, respectively, whereas in brain, NOR was detected only at doses greater than or equal to 10 mg/kg (approximately 5.6% of CLZ) and NOX was undetectable. Levels peaked within 30 minutes, and elimination of CLZ from brain and CLZ or NOR from blood was very rapid (half-life = 1.5 to1.6 hours). A week of daily dosing with CLZ led to no accumulation ofdrug.in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect.

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Documento generato il 26/01/20 alle ore 00:43:18