Pharmacopsychiatry 2018; 51(03): 112
DOI: 10.1055/s-0038-1649536
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

The effect of pharmacological interaction between a proton pump inhibitor pantoprazole and clozapine

M Kuzin
1   Psychiatric Services of Thurgovia, Academic Teaching Hospital of the Medical University of Salzburg, Münsterlingen, Switzerland
,
G Schoretsanitis
2   Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
3   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA – Translational Brain Medicine, Jülich, Germany
,
E Haen
4   Clinical Pharmacology at the Department of Psychiatry and Psychotherapy and at the Department of Pharmacology and Toxicology, University of Regensburg, Germany
,
G Dammann
1   Psychiatric Services of Thurgovia, Academic Teaching Hospital of the Medical University of Salzburg, Münsterlingen, Switzerland
,
C Hiemke
5   Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany
,
G Gründer
6   Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
M Paulzen
3   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA – Translational Brain Medicine, Jülich, Germany
7   Alexianer Hospital Aachen, Alexianergraben 33, 52062, Aachen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
09 May 2018 (online)

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Background:

Polypharmacy including psychotropic agents as well as somatic drugs such as proton pump inhibitors (PPIs) may increase the risk of drug-drug interactions. Cytochrome P450 (CYP) 1A2 plays a central role in the oxidative metabolism of clozapine (CLZ), with additional involvement of CYP2C19, 3A4 and 2D6 to varying degrees. Pantoprazole (PANTO) has inhibitory properties on CYP2C19. The aim of this study was the evaluation of pharmacokinetic interactions between PANTO and 2C19-mediated metabolism of CLZ using therapeutic drug monitoring (TDM).

Methods:

A large TDM database containing plasma concentrations of CLZ (n = 1644) was analyzed. The results were stratified in four groups: a non-smokers (n = 250) and a smokers group (n = 326) with clozapine monotherapy, a non-smokers (n = 26) and a smokers (n = 29) group co-medicated with pantoprazole. Histograms yielded evidence of non-normal distribution of the data, so that a non-parametrical Mann Whitney U test (M-W-U) with a significance level of 0.05 was applied.

Results:

In smokers and non-smokers no differences between CLZ monotherapy and co-medication with PANTO for demographic/pharmacokinetic parameters were observed (p > 0.05 for M-W-U in all cases). In monotherapy patients, when comparing smokers with non-smokers, the daily dosage of CLZ was significantly higher in the group of smokers (363.38 (SD = 181.17) vs. 290.52 (SD = 144.73)mg/day, p < 0.001 for M-W-U).

Conclusions:

In contrast to omeprazole, the combination of clozapine with pantoprazole does not lead to pharmacokinetic interactions. The difference between the two PPIs may be related to the extent of inhibition of CYP2C19-mediated clozapine metabolism.