| Literature DB >> 8216694 |
R J Baldessarini1, F Centorrino, J G Flood, S A Volpicelli, D Huston-Lyons, B M Cohen.
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 to 1.6 hours). A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect.Entities:
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Year: 1993 PMID： 8216694 DOI： 10.1038/npp.1993.50
Source DB: PubMed Journal: Neuropsychopharmacology ISSN： 0893-133X Impact factor: 7.853