Higher than expected clozapine serum level and clozapine/norclozapine ratio due to CYP450 gene polymorphisms

Dorgival Caetano; Irina Piatkov

doi:10.2217/pme.15.33

Higher than expected clozapine serum level and clozapine/norclozapine ratio due to CYP450 gene polymorphisms

Per Med. 2015 Nov;12(6):555-558. doi: 10.2217/pme.15.33. Epub 2015 Nov 6.

Authors

Dorgival Caetano^{1

2}, Irina Piatkov²

Affiliations

¹ Blacktown Mental Health Service, WSLHD, Blacktown, NSW, 2148, Australia.
² Blacktown Clinical School & Research Centre, WSLHD, Blacktown, NSW, 2148, Australia.

PMID: 29750612
DOI: 10.2217/pme.15.33

Abstract

Aims: We investigated a case of the unexpectedly high clozapine/norclozapine serum levels in a non-smoker, female patient.

Method: The RFLP genotype method was used for the loss-of-function CYP450 gene polymorphisms detection.

Results: The genotype revealed the presence of CYP2D6*41/*41, rs28371725, NM_000106.5:c.985+39G>A and CYP1A2*1/*1D rs35694136, NM_000761.4:c.-1635delT.

Conclusion: An appropriate clozapine serum level is required for both optimization of clinical response and avoidance of troublesome, or even life-threatening side effects. Although not the only factor, genetic polymorphisms responsible for the metabolism of clozapine play an important role towards such goals. Pharmacogenetic tests can guide dose adjustment in order to obtain an optimum serum level, which can lead to a better therapeutic response and minimization of harmful side effects.

Keywords: CYP1A2; CYP2D6; CYP450; clozapine; pharmacogenetics.