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. 2022 May;19(3):181-192.
doi: 10.2217/pme-2021-0029. Epub 2022 Mar 9.

Exploring the usefulness of plasma level determination and pharmacogenetics for patients treated with clozapine

Estela Sangüesa  1 , Christine Cirujeda  2 , Julia Concha  1 , Pedro Pablo Padilla  2 , Cristina Belén García  1 , María Pilar Ribate  1
Affiliations

Exploring the usefulness of plasma level determination and pharmacogenetics for patients treated with clozapine

Estela Sangüesa et al. Per Med. 2022 May.

Abstract

Aims: The aims of the present study were to assess the variance of plasma clozapine (CLZ) levels and to identify the influence of sociodemographic and pharmacogenetic factors on it and to introduce these tools in a clinical setting. Patients & methods: CLZ concentration was measured and genetic variants of CLZ pharmacokinetic and pharmacodynamic factors were assessed in 23 patients with psychotic disorders. Results: A significant association between mean concentration/dose ratio (C/D) and smoking status, age and weight were found. There was a significant difference in mean plasma CLZ levels and gender. The rs762551 AA genotype in smokers had a significantly lower C/D. Conclusion: In addition to classical factors, monitoring of plasma concentrations together with pharmacogenetics led to greater individualization of treatment.

Keywords: CYP1A2; clozapine; individualized therapy; interactions; norclozapine; pharmacogenetics; polypharmacy; psychotic disorders; smoking status; therapeutic drug monitoring.

Plain language summary

Patients receiving clozapine (CLZ) usually show a variability in plasma concentrations. This study assesses the variance of plasma CLZ levels and explores the influence of gender, smoking, age, weight and genetics. Plasma CLZ levels were measured in 23 patients with psychotic disorders. Additionally, genetic analysis of genes involved in CLZ metabolism were carried out. An association between plasma concentration of CLZ adjusted for daily dose and smoking status, weight and age were found. Plasma CLZ and gender were also associated. A mutation of a genetic variant related to CLZ metabolism showed in smokers lower CLZ concentration adjusted for daily dose, explaining poor treatment response. Individual dose modification in these patients improved the clinical situation.

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