ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine

Jaquenoud Sirot, Eveline; Knezevic, Branka; Morena, Gina Perla; Harenberg, Sabine; Oneda, Beatrice; Crettol, Severine; Ansermot, Nicolas; Baumann, Pierre; Eap, Chin B

doi:10.5167/uzh-192538

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Jaquenoud Sirot, E., Knezevic, B., Morena, G. P., Harenberg, S., Oneda, B., Crettol, S., Ansermot, N., Baumann, P., & Eap, C. B. (2009). ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. Journal of Clinical Psychopharmacology, 29, 319–326. https://doi.org/10.1097/JCP.0b013e3181acc372

Abstract

To examine the genetic factors influencing clozapine kinetics in vivo, 75 patients treated with clozapine were genotyped for CYPs and ABCB1 polymorphisms and phenotyped for CYP1A2 and CYP3A activity. CYP1A2 activity and dose-corrected trough steady-state plasma concentrations of clozapine correlated significantly (r = -0.61; P = 1 x 10), with no influence of the CYP1A2*1F genotype (P = 0.38). CYP2C19 poor metabolizers (*2/*2 genotype) had 2.3-fold higher (P = 0.036) clozapine concentrations than the extensive metabolizers (non-*2/*2).