CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients

  • Doude Van Troostwijk L
  • Koopmans R
  • Vermeulen H
 et al. 
  • 33


    Mendeley users who have this article in their library.
  • 33


    Citations of this article.


Clozapine is an effective atypical antipsychotic drug applied in the treatment of resistant schizophrenia. The drug is mainly metabolized by cytochrome P-450 (CYP) enzymes especially the isozyme CYP1A2. Remarkably, the effective dosage varies widely among patients, making it necessary to individualize drug therapy with clozapine. The explanation for dosage variation may be differences in drug metabolism, and more specifically of CYP1A2 activity. This study is aimed at determining to what extent variability in clozapine dose can be explained by pharmacokinetic (PK) factors and more specifically by CYP1A2 activity in effectively treated psychiatric patients. In 22 evaluable patients with a schizophrenic disorder chronically using clozapine, the CYP1A2 activity and the clozapine clearance were estimated. For calculation of the pharmacokinetic parameters of clozapine, population PK software based upon Bayesian analysis was used. Caffeine clearance was estimated with the paraxanthine/caffeine ratio and served as estimate of CYP1A2 activity. A significant linear relationship was found between the clozapine dose and clozapine clearance (R: 0.71; P

Author-supplied keywords

  • CYP1A2 activity
  • Clozapine dose
  • Clozapine metabolism
  • Pharmacokinetics

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Lous J.A.E. Doude Van Troostwijk

  • Richard P. Koopmans

  • Hans D.B. Vermeulen

  • Henk Jan Guchelaar

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free