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Objective:To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration, so as to provide reference for individualized treatment.Methods:Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory (TDM) of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021, and information such as patient gender, age, body mass index (BMI), smoking history, clozapine dose, combined drug use and blood concentration monitoring results were collected; Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results:Among 221 monitoring reports, 74 cases (normal concentration group) had clozapine plasma concentration within the effective plasma concentration range (350-600 ng/ml), 103 cases (low concentration group) were lower than the effective plasma concentration range (<350 ng/ml), and 44 cases (high concentration group) were higher than the effective plasma concentration range (>600 ng/ml). The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine, standard dose, smoking history, course of disease, and abnormal liver function of patients in different blood concentration groups of clozapine (all P<0.05). The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate, amisulpride, aripiprazole and lithium carbonate in turn. The proportion of clozapine combined with ≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and ≥ two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration (350-600 ng/ml), and the combination of two drugs was more beneficial [ OR(95% CI): 1.795(0.753-4.282)], with a statistically significant difference ( P<0.05). Conclusions:Clozapine plasma concentration varies greatly among individuals, and the therapeutic window is narrow. It is necessary to adjust the dosage in combination with the basic information and clinical information of patients, and regularly monitor the plasma concentration, so as to achieve the safety and effectiveness of individualized drug use.
RESUMO
OBJECTIVE To explore the relationship between the ANKK1 rs1800497 polymorphism and atypical antipsychotic drug-induced metabolic syndrome （MS）. METHODS Totally 94 patients with schizophrenia were included， and ANKK1 rs1800497 genotypes of patients were detected by micro-fluorescence immunoassay； social demographic information， clinical characteristics and other data were collected. The χ2 test was used to compare the correlation between the sex of patients and the occurrence of MS， and the correlation between gene polymorphism and the occurrence of MS and its risk factors.RESULTS Totally 94 patients included 24 cases （25.53%） of GG， 51 cases （54.26%） of GA and 19 cases of AA （20.21%）. Among them， there were 45 cases （47.87%） of MS， and the incidence of MS in male was higher than that in female （P＜0.05）. Genotype analysis showed that ANKK1 rs1800497 polymorphism was not associated with MS （P＝0.452）. ANKK1 rs1800497 A allele was significantly associated with hyperglycemia （χ2＝4.379， P＝0.036）， while it was not related to abdominal obesity， hypertension， high level of TG and low level of HDL-C （P＞0.05）， suggesting that for patients with schizophrenia， allele A was a relative risk factor for inducing hyperglycemia [OR＝2.008，95%CI（1.039， 3.881）]. CONCLUSIONS ANKK1 rs1800497 polymorphism has no correlation with the induction of MS by atypical antipsychotics， while the schizophrenia patients with A allele are more likely to induce hyperglycemia. The incidence of MS in male patients is significantly higher than that in female patients.