CYP2C19*17 protects against metabolic complications of clozapine treatment
| Autor: | Micheline Coelho, Tristan Nguyen, Mark McLean, Yolinda Assur, Steven C. Boyages, Irina Piatkov, Trudi Jones, Sue Lynn Lau, Dorgival Caetano |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Drug media_common.quotation_subject CYP2C19 Pharmacology 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Outcome Assessment Health Care Diabetes Mellitus medicine Humans Adverse effect Clozapine Biological Psychiatry Schizophrenic disorders media_common Glycated Hemoglobin business.industry Middle Aged Protective Factors medicine.disease Cytochrome P-450 CYP2C19 Psychiatry and Mental health 030220 oncology & carcinogenesis Schizophrenia Female medicine.symptom business Weight gain 030217 neurology & neurosurgery Drug metabolism Antipsychotic Agents medicine.drug |
| Zdroj: | The World Journal of Biological Psychiatry. 18:521-527 |
| ISSN: | 1814-1412 1562-2975 |
| Popis: | Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients.We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and norclozapine (NCZ) levels, and clinical outcomes.Thirty-nine percent of genotyped patients were carriers of the CYP2C 19*17 polymorphism. This group demonstrated significantly higher NCZ serum levels, and significantly lower fasting glucose (5.66 ± 1.19 vs 6.72 ± 3.01 mmol/l, P = 0.009) and Hb1Ac (35.36 ± 4.78 vs 49.40 ± 20.60 mmol/mol, P = 0.006) levels compared to non-carriers of this polymorphism. CZ-treated patients with CYP2C19*17/*17 had a significantly lower prevalence of diabetes as well as a higher likelihood of clinical improvement of their schizophrenia, compared to those without this polymorphism (P = 0.012 and P = 0.031, respectively).Our data suggest that CYP2C19*17 ultra-rapid-metaboliser status is a protective factor against the development of diabetes during clozapine treatment, and increases the likelihood of improvement in schizophrenia. The role of NCZ in treatment response and side effects, including metabolic syndrome, warrants further pharmacogenetic, pharmacokinetic and pharmacodynamic studies. |
| Databáze: | OpenAIRE |
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