Tissue concentrations of clozapine and its metabolites in the rat
| Autor: | Bruce M. Cohen, James G. Flood, David Huston-Lyons, Sheila A. Volpicelli, Franca Centorrino, Ross J. Baldessarini |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Metabolite Intraperitoneal injection Pharmacology Mass Spectrometry Rats Sprague-Dawley chemistry.chemical_compound Pharmacokinetics Internal medicine Fluoxetine medicine Animals Antipsychotic Clozapine Valproic Acid business.industry Half-life Brain Metabolism Rats Psychiatry and Mental health Endocrinology chemistry business medicine.drug Half-Life |
| Zdroj: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 9(2) |
| ISSN: | 0893-133X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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