Clozapine Metabolism in East Asians and Caucasians: A Pilot Exploration of the Prevalence of Poor Metabolizers and a Systematic Review

Journal of Clinical Psychopharmacology
Can-Jun RuanJose de Leon

Abstract

In clozapine therapeutic drug monitoring (TDM) studies, Chinese reached the same concentrations using half the dosage Caucasians use. Defining clozapine poor metabolizers (PMs) requires stratification by ethnicity, smoking, and sex. After sex and smoking stratification in 129 Chinese inpatients (mean, 8.8 TDM samples per patient), we explored the association between the total concentration-dose (C/D) ratio and CYP1A2 (*1C, *1F, and *7) and CYP2C19 alleles (*2 and *3). A systematic literature review identified 22 clozapine TDM prior studies (13 in Caucasians and 7 in East Asians). In our Chinese sample, the mean total clozapine C/D ratio (ng/mL per mg/d) was 1.96 for 22 male smokers, 2.07 for 5 female smokers, 2.47 for 36 male nonsmokers, and 2.95 for 66 female nonsmokers. CYP1A2 *1C had no significant effects, and CYP1A2 *1F had small effects. Five clozapine PMs (4%) needed low clozapine doses of 75 to 115 mg/d to get therapeutic concentrations. Using the same methodology in a published Italian sample, we found 5 PMs (3.3% of 152). In the systematic review, the clozapine C/D ratio (ng/mL per mg/d) was higher when comparing: (1) weighted mean values of 1.57 in 876 East Asians versus 1.07 in 1147 Caucasians and (2) ranks of 8 Eas...Continue Reading

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Citations

Mar 3, 2020·Asia-Pacific Psychiatry : Official Journal of the Pacific Rim College of Psychiatrists·Jose de LeonCan-Jun Ruan
Apr 21, 2020·Pharmacogenomics·Can-Jun Ruan, Jose de Leon
Apr 26, 2020·Journal of Clinical Psychopharmacology·Georgios SchoretsanitisJose de Leon
Jan 31, 2020·Indian Journal of Psychological Medicine·Michael W Jann
May 19, 2020·General Psychiatry·Jose de LeonChuanyue Wang
Oct 2, 2020·Clinical Pharmacokinetics·Georgios SchoretsanitisEkkehard Haen
Jun 18, 2019·Journal of Clinical Psychopharmacology·Jaqueline BarclayJose de Leon
Dec 5, 2020·Acta Psychiatrica Scandinavica·Yuji YadaNorihito Yamada
Feb 16, 2021·Journal of Clinical Psychopharmacology·Georgios SchoretsanitisJose de Leon
Dec 2, 2020·Revista de psiquiatrí́a y salud mental·Dinora F González-EsquivelJose de Leon
Aug 31, 2021·Revista De Psiquiatria Y Salud Mental·Dinora F González-EsquivelJose de Leon
Apr 15, 2020·Psychotherapy and Psychosomatics·Jose de LeonCarlos De Las Cuevas

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