Article date: May 2002
By: E. J. Mookhoek, A. J. M. Loonen, in Volume 53, Issue 5, pages 545P-545P
Many chronic psychiatric inpatients suffer from schizophrenia and gastric disorders. Some of them are therefore treated with a combination of clozapine and an acid pump inhibitor. The atypical antipsychotic clozapine is metabolized by CYP1A2, CYP3A4 and CYP2D6. The acid pump inhibitor omeprazole can inhibit the activity of CYP2C19 and induce the activity of CYP2C8‐9, CYP3A4 and CYP1A2. The acid pump inhibitor pantoprazole is largely devoid of these activities. The possibility of pharmacokinetic drug drug interactions with psychotropic drugs lead in Spring 2000 to the replacement of omeprazole by pantoprazole in the drug formulary of Delta Psychiatric Hospital. In this hospital the plasma concentrations of clozapine and its primary metabolite are measured at regular intervals on a routine basis. This offers the opportunity to investigate the possible consequences of the change of acid pump inhibitor.
The aim was to retrospectively assess the possible effect of the change of omeprazole to pantoprazole on the plasma concentrations of clozapine.
The medication records of all long‐stay psychiatric in‐patients were checked and those patients were selected who used omeprazole and clozapine on April 4, 2000 and who were changed to pantoprazole for the rest of the year. The medical records of these patients were searched for data on clozapine plasma concentrations before and at least 6 weeks after the change, necessary changes of the clozapine dosage due to a changed clinical condition, and possibly reported adverse events. The data were controlled for co‐medication that influences the activity of CYP isoforms and for smoking habits.
Out of 430 long‐stay patients 49 used omeprazole and 15 also used clozapine. Of these, 13 were finally evaluable. The 13 patients used 423±153.6 mg clozapine per day (mean±s.d.). Before the change, the clozapine concentrations measured 382±190.6 µg l−1. After the change, these concentrations measured 382±158.9 µg l−1. In five patients an increase in plasma concentrations was observed. Three of them were non‐smokers. A significant correlation (Pearson Rank, −0.615, P=0.025) was found between the second clozapine concentration and the amount of tobacco smoked per day. There existed no reports of changes in the medical condition, particularly the occurrence of relevant adverse events, that could be attributed to a change in clozapine plasma concentrations.
No relevant changes were observed retrospectively in the plasma concentrations and clinical effects of clozapine due to the alteration of omeprazole to pantoprazole in this small patient population. However, there appears to exist a relationship between the smoking habits and the sensitivity to this change. This might be due to the CYP inducing activity of tobacco smoke, which may be more important than the CYP inducing activity of omeprazole.
DOI: 10.1046/j.1365-2125.2002.16135.x
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