Clozapine Monitoring: Plasma or Serum Levels?

In this study, differences between plasma and serum levels of clozapine and norclozapine were quantified and correlations of these differences with myeloperoxidase (MPO) activities were examined. Fifty-seven patients (34 men and 23 women, mean age 36.6+/-11.4 years) taking clozapine in a daily doses varying from 75 to 800 mg entered the study. All patients were analyzed for clozapine level, 29 were analyzed for norclozapine level and 28 for MPO activity. Significant differences (p<0.001) between plasma and serum levels were found for clozapine (mean decrease 9.99+/-15.8%) and norclozapine (mean decrease 16.0+/-21.2%) and for MPO activities (mean increase 114.1+/-123.9%). No correlation was found between differences of MPO activities and differences of drug levels in plasma and serum. Differences in clozapine and norclozapine levels could reflect chemical instability of these drugs. These compounds should be quantified only in plasma because serum levels underestimate blood levels in patients.