Clozapine pharmacokinetics and pharmacodynamics studied with Cyp1A2-null mice.

摘要: The aim of this study was to use the CYP1A2-null mouse investigate in-vivo contribution CYP1A2 clozapine pharmacokinetics and pharmacodynamics. An intraperitoneal injection 10 mg/kg administered four male -/- mice wild-type mice. Clozapine, desmethylclozapine, N-oxide concentrations in sequential tail blood samples were measured by HPLC with UV detection. Behavioural parameters recorded at each time point. area under curve (AUC) 2.6 times greater, clearance slower, half-life 1.2 longer (p = 0.0143) as compared Sixty-one percent calculated be mediated CYP1A2. AUC desmethylclozapine 1.6 lower 0.0286), while there a trend for greater 0.0571). significantly more drowsy showed motor impairment 0.0145) myoclonus than Our results indicate that, vivo, is major determinant clearance, contributes demethylation clozapine, has negligible N-oxidation. data also that poor metabolizers might susceptible extensive dose-related adverse effects such sedation, seizures.