한국인 조현병 환자에서 클로자핀 처방용량과 혈중농도의 관계 및 이에 영향을 미치는 요인에 관한 연구
Clozapine Dose-Concentration Relationship and Other Factors Associated With Clozapine Plasma Concentration in Korean Schizophrenia Patients
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives: Some reports suggest that the concentration-to-dosage ratio (C/D ratio) of clozapine (CZP) in Asian treatment-resistant schizophrenia (TRS) patients differs from that of Caucasian TRS patients. However, there is insufficient research on the differences in C/D ratio between Korean TRS patients and Caucasian TRS patients. Therefore, this study aimed to investigate prescribed CZP dosage, CZP concentration and C/D ratio in Korean TRS patients.Methods: The study included TRS patients aged 18 years or older who were prescribed CZP for at least 12 weeks at a psychiatric hospital in Korea. We collected demographic information, smoking status, hospitalization status, CZP serum concentration, total CZP dosage, and norclozapine (NCZP) serum concentration and analyzed their statistical correlations.Results: The study found that the average daily CZP dosage was 266.1 mg, and the average CZP concentration was 568.0 ng/mL. There was a significant correlation between CZP serum concentration and smoking status, as well as sex. CZP dosage was not significantly associated with age, weight, BMI, or metabolic rate. The study also found a significant difference in C/D ratio between groups based on CZP serum concentration.Conclusion: Our study suggests that recommended CZP dosages for Caucasians may not be suitable for Koreans due to C/D ratio differences. We found a relationship between CZP serum concentration and C/D ratio in Korean TRS patients. Therefore, it is crucial to confirm CZP serum concentration to avoid side effects and to find optimal dosage.
Abstract
Objectives: Some reports suggest that the concentration-to-dosage ratio (C/D ratio) of clozapine (CZP) in Asian treatment-resistant schizophrenia (TRS) patients differs from that of Caucasian TRS patients. However, there is insufficient research on the differences in C/D ratio between Korean TRS patients and Caucasian TRS patients. Therefore, this study aimed to investigate prescribed CZP dosage, CZP concentration and C/D ratio in Korean TRS patients.Methods: The study included TRS patients aged 18 years or older who were prescribed CZP for at least 12 weeks at a psychiatric hospital in Korea. We collected demographic information, smoking status, hospitalization status, CZP serum concentration, total CZP dosage, and norclozapine (NCZP) serum concentration and analyzed their statistical correlations.Results: The study found that the average daily CZP dosage was 266.1 mg, and the average CZP concentration was 568.0 ng/mL. There was a significant correlation between CZP serum concentration and smoking status, as well as sex. CZP dosage was not significantly associated with age, weight, BMI, or metabolic rate. The study also found a significant difference in C/D ratio between groups based on CZP serum concentration.Conclusion: Our study suggests that recommended CZP dosages for Caucasians may not be suitable for Koreans due to C/D ratio differences. We found a relationship between CZP serum concentration and C/D ratio in Korean TRS patients. Therefore, it is crucial to confirm CZP serum concentration to avoid side effects and to find optimal dosage.
참고문헌 (30)
- Lewis SW, "Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia", Schizophr Bull, 32, pp.715~723 (2006)
- McEvoy JP, "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment", Am J Psychiatry, 163, pp.600~610 (2006)
- Keepers GA, "The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia", AJP, 177, pp.868~872 (2020)
- Barnes TR, "Evidence-based guidelines for the pharmacological treatment of schizophrenia : Updated recommendations from the British Association for Psychopharmacology", J Psychopharmacol, 34, pp.3~78 (2020)
- Hiemke C, "AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry : Update 2011", Pharmacopsychiatry, 44, pp.195~235 (2011)
- Spina E, "Clinical applications of CYP genotyping in psychiatry", J Neural Transm(Vienna), 122, pp.5~28 (2015)
- Perry PJ, "Clozapine and norclozapine plasma concentrations and clinical response of treatmentrefractory schizophrenic patients", Am J Psychiatry, 148, pp.231~235 (1991)
- Hasegawa M, "Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia : effect of smoking", J Clin Psychopharmacol, 13, pp.383~390 (1993)
- Wetzel H, "Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors : differential effects of fluvoxamine and paroxetine in a prospective study", J Clin Psychopharmacol, 18, pp.2~9 (1998)
- Ruan CJ, "Clozapine Metabolism in East Asians and Caucasians : a Pilot Exploration of the Prevalence of Poor Metabolizers and a Systematic Review", Journal of Clinical Psychopharmacology, 39, pp.135~ (2019)
- Ng CH, "An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels", International Clinical Psychopharmacology, 20, pp.163~168 (2005)
- 강시현, "클로자핀 처방 패턴 및 클로자핀 중단과 관련된 임상 요인", 대한조현병학회지, 22(1), pp.2~7 (2019), 대한조현병학회[DOI]
- Iglesias García C, "Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients", Rev Psiquiatr Salud Ment, 10, pp.192~196 (2017)
- Reeves S, "A population pharmacokinetic model to guide clozapine dose selection, based on age, sex, ethnicity, body weight and smoking status", Br J Clin Pharmacol, pp.1~11 (2023)
- Albitar O, "Population Pharmacokinetics of Clozapine : A Systematic Review", Biomed Res Int, 2020, pp.9872936~ (2020)
- Smith RL, "Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients—a genome-wide association study adjusting for smoking habits", Transl Psychiatry, 10, pp.1~10 (2020)
- McGraw J, "Cytochrome P450 variations in different ethnic populations", Expert Opin Drug Metab Toxicol, 8, pp.371~382 (2012)
- Qurashi I, "Changes in smoking status, mental state and plasma clozapine concentration: retrospective cohort evaluation", BJPsych Bull, 43, pp.271~274 (2019)
- Rostami-Hodjegan A, "Influence of Dose, Cigarette Smoking, Age, Sex, and Metabolic Activity on Plasma Clozapine Concentrations:A Predictive Model and Nomograms to Aid Clozapine Dose Adjustment and to Assess Compliance in Individual Patients", Journal of Clinical Psychopharmacology, 24, pp.70~78 (2004)
- Tsai YW, "Gender Differences in Smoking Behaviors in an Asian Population", J Womens Health(Larchmt), 17, pp.971~978 (2008)
- Cao XL, "Current cigarette smoking in Chinese female patients with schizophrenia : A meta-analysis", Psychiatry Research, 235, pp.203~205 (2016)
- Xu YM, "Prevalence and Correlates of Cigarette Smoking among Chinese Schizophrenia Inpatients Receiving Antipsychotic Mono-Therapy", PLOS ONE, 9, pp.e88478~ (2014)
- Willcocks IR, "Clozapine Metabolism is Associated With Absolute Neutrophil Count in Individuals With Treatment-Resistant Schizophrenia", Front Pharmacol, 12, pp.658734~ (2021)
- Schoretsanitis G, "A comprehensive review of the clinical utility of and a combined analysis of the clozapine", norclozapine ratio in therapeutic drug monitoring for adult patients, 2019, pp.12, 603~621
- Couchman L, "Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: data from a therapeutic drug monitoring service, 1994-2010: Plasma clozapine: patients aged <18 years", Early Intervention in Psychiatry, 7, pp.122~130 (2013)
- Kuzin M, "Body mass index as a determinant of clozapine plasma concentrations : A pharmacokinetic-based hypothesis", J Psychopharmacol, 35, pp.273~278 (2021)
- Ismail Z, "Age and sex impact clozapine plasma concentrations in inpatients and outpatients with schizophrenia", Am J Geriatr Psychiatry, 20, pp.53~60 (2012)
- Castberg I, "Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine", Acta Psychiatr Scand, 136, pp.455~464 (2017)
- Lane HY, "Effects of gender and age on plasma levels of clozapine and its metabolites : analyzed by critical statistics", J Clin Psychiatry, 60, pp.36~40 (1999)
- Ulrich S, "Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data", Int J Clin Pharmacol Ther, 41, pp.3~13 (2003)
