Merve Demirbugen Oz, Fezile Ozdemir, Kenan Can Tok, Emrah Dural, Yagmur Kir, Muge Ulusoy, Mehmet Gumustas, Bora Baskak, H Sinan Suzen
{"title":"POR*28和CYP1A2*F遗传变异和生活方式因素对精神分裂症患者氯氮平和n -去甲基氯氮平血浆水平的潜在作用","authors":"Merve Demirbugen Oz, Fezile Ozdemir, Kenan Can Tok, Emrah Dural, Yagmur Kir, Muge Ulusoy, Mehmet Gumustas, Bora Baskak, H Sinan Suzen","doi":"10.1080/17425255.2023.2221849","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects.</p><p><strong>Research design and methods: </strong>As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method.</p><p><strong>Results: </strong>The patients' <i>CYP1A2</i> and <i>POR</i> genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis, <i>POR *28</i> genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption.</p><p><strong>Conclusions: </strong>The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making.</p>","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"19 5","pages":"319-327"},"PeriodicalIF":3.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Potential Role of <i>POR*28</i> and <i>CYP1A2*F</i> Genetic Variations and Lifestyle Factors on Clozapine and N-DesmethylClozapine Plasma Levels in Schizophrenia Patients.\",\"authors\":\"Merve Demirbugen Oz, Fezile Ozdemir, Kenan Can Tok, Emrah Dural, Yagmur Kir, Muge Ulusoy, Mehmet Gumustas, Bora Baskak, H Sinan Suzen\",\"doi\":\"10.1080/17425255.2023.2221849\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects.</p><p><strong>Research design and methods: </strong>As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method.</p><p><strong>Results: </strong>The patients' <i>CYP1A2</i> and <i>POR</i> genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis, <i>POR *28</i> genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption.</p><p><strong>Conclusions: </strong>The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. 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The Potential Role of POR*28 and CYP1A2*F Genetic Variations and Lifestyle Factors on Clozapine and N-DesmethylClozapine Plasma Levels in Schizophrenia Patients.
Background: Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects.
Research design and methods: As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method.
Results: The patients' CYP1A2 and POR genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis, POR *28 genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption.
Conclusions: The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making.
期刊介绍：
Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
The Editors welcome:
Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data.
Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug.
The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.
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