Exploring the Prevalence of Clozapine Phenotypic Poor Metabolizers in 4 Asian Samples: They Ranged Between 2% and 13%

Ruan, Can-Jun; Wang, Chuan-Yue; Tang, Yi-Lang; Lin, Shih-Ku; Lee, Seung-Tae; Hong, Kyung Sue; Rajkumar, Anto P.; Jacob, Kuruthukulangara S.; De Leon, Jose

Abstract

Purpose/Background: Clozapine clearance is influenced by sex, smoking status, ethnicity, co-prescription of inducers or inhibitors, obesity and inflammation. In 126 Beijing inpatients, we measured repeated trough steady-state serum concentrations and identified 4% (5/126) who were phenotypical poor metabolizers (PMs); none were ultrarapid metabolizers (UMs). They were defined as being 2 standard deviations beyond the means of total clozapine concentration/dose ratios stratified by sex and smoking. Using this definition, this study explores the prevalences of PMs and UMs using data from 4 already-published Asian samples. Three samples were East Asian (Beijing 2, Taipei and Seoul); one was from South India (Vallore).

Findings/Results: The prevalence of phenotypical PMs ranged from 2-13%, but inflammation was not excluded. The prevalence was 7.3% (14/191) for Beijing 2, 11% (8/70) for Taipei, 13% (9/67) for Seoul, and 2% (2/101) for the Vellore sample. Five phenotypical PMs appeared to be associated with extreme obesity. Phenotypic UM prevalence ranged from 0-1.6%, but may be partly explained by lack of adherence. A Vellore phenotypic UM appeared to be associated with induction through high coffee intake.

Implications/Conclusions: Around 10% of Asians may be clozapine PMs and may only need 50-150 mg/day to get therapeutic concentrations. Future studies combining gene sequencing for new alleles with repeated concentrations and careful control of confounders including inhibitors, inflammation and obesity should provide better estimations of the prevalence of phenotypic clozapine PMs across races. Clozapine UM studies require excluding potent inducers, careful supervision of compliance in inpatient settings and multiple serum concentrations.

Citation

Ruan, C.-J., Wang, C.-Y., Tang, Y.-L., Lin, S.-K., Lee, S.-T., Hong, K. S., Rajkumar, A. P., Jacob, K. S., & De Leon, J. (2019). Exploring the Prevalence of Clozapine Phenotypic Poor Metabolizers in 4 Asian Samples: They Ranged Between 2% and 13%. Journal of Clinical Psychopharmacology, 39(6), 644-648. https://doi.org/10.1097/JCP.0000000000001125

• Journal Article Type: Article
• Acceptance Date: Aug 19, 2019
• Online Publication Date: Nov 1, 2019
• Publication Date: 2019-11
• Deposit Date: Sep 5, 2019
• Publicly Available Date: Nov 2, 2020
• Print ISSN: 0271-0749
• Electronic ISSN: 1533-712X
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 6
• Pages: 644-648
• DOI: https://doi.org/10.1097/JCP.0000000000001125
• Public URL: https://nottingham-repository.worktribe.com/output/2571498
• Publisher URL: https://journals.lww.com/psychopharmacology/Abstract/2019/11000/Exploring_the_Prevalence_of_Clozapine_Phenotypic.19.aspx
• Contract Date: Sep 5, 2019