Objective  To analyze the current status of blood concentration monitoring in patients using risperidone orally in a grade A psychological hospital, and to explore the objective factors affecting the blood concentration of risperidone.

Methods  All the results of risperidone serum concentration with oral administration and related patient infor-mation and case data in the hospital from May, 2019 to July, 2019 were collected. Retrospective analysis was used to explore the relationship between daily dose administered, body mass index (BMI), age, gender, combined medications and blood concentration, and data related to blood concentration in different populations.

Results  Pharmacokinetic data from 299 inpatients met inclusion criteria, with 62.88% demonstrating risperidone concentrations within the therapeutic reference concentration range (20-60 ng·mL^-1). The median valece of risperidone concentrations and doses were lower in geriatric (≥60 years) versus young and middle-aged patients (both P<0.01), though no differences in metabolizing capacity were observed by age or sex. The administered dose and median blood concentration in low body weight patients showed no statistically significant difference compared to patients with normal, overweight and obese body weight, while the me-tabolite/parent drug ratio was higher than that of patients with normal, overweight and obese body weight (P<0.001). The daily dosage of female patients was lower than that of male patients (P=0.01). The concentration/dosage ratio of female patients was higher than that of male patients (P<0.001). The concentration/dosage ratio was consistent with the results comparing male and female patients in both elderly (P=0.04) and non-elderly (P<0.001) groups, with the difference being statistically significant. The metabolite/parent drug ratio of patients combined valproate therapy was higher than that of patients treated with risperidone alone (P=0.003). The median value of combined medications was 1 in the group with blood concentration below the lower limit of the therapeutic range, and was 0 in the group above the upper limit, with statistically significant difference (P=0.023).  Conclusion  Age, dose, gender, BMI and combination of medications can di-rectly or indirectly affect the MPR of patients. Patients with a BMI below the normal range may inhibit the metabolic process of risperidone. The physiological differences in female patients and the combination of sodium valproate may also affect the metabolism of risperidone in the body.

1.邵岩, 姚贵忠. 精神分裂症的康复与长期治疗[J]. 中华精神科杂志, 2018, 51(1): 71-72. [Shao Y, Yao GZ. Recov-ery and long-term treatment of schizophrenia[J]. Chinese Journal of Psychiatry, 2018, 51(1): 71-72.] DOI: 10.3760/cma.j.issn.1006-7884.2018.01.019.

2.Charlson FJ, Ferrari AJ, Santomauro DF, et al. Global epidemiology and burden of schizophrenia: find-ings from the global burden of disease study 2016[J]. Schizophr Bull, 2018, 44(6): 1195-1203. DOI: 10.1093/schbul/sby058.

3.Zhong Q, Tan Y, Chen W, et al. Disease burden of schizophrenia patients visiting a Chinese regional mental health centre[J]. J Comp Eff Res, 2020, 9(7): 469-481.DOI: 10.2217/cer-2019-0129.

4.Nicotra EF, Lecca D, Casu G, et al. Lights and shadows of schizophrenia therapy research: lessons from oral risperidone and olanzapine[J]. J Psychopharmacol, 2020, 34(5): 574-579. DOI: 10.1177/0269881119900980.

5.Carrascal-Laso L, Isidoro-Garcia M, Ramos-Gallego I, et al. Review: influence of the CYP450 genetic variation on the treatment of psychotic disorders[J]. J Clin Med, 2021, 10(18): 4275. DOI: 10.3390/jcm10184275.

6.Vandenberghe F, Najar-Giroud A, Holzer L, et al. Second-generation antipsychotics in adolescent psy-chiatric patients: metabolic effects and impact of an early weight change to predict longer term weight gain[J]. J Child Adolesc Psychopharmacol, 2018, 28(4): 258-265. DOI: 10.1089/cap.2017.0038.

7.Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017[J]. Pharmacopsychiatry, 2018, 51(1-02): e1. DOI: 10.1055/s-0037-1600991.

8.中国药理学会治疗药物监测研究专业委员会, 中国医师协会精神科医师分会, 中国药理学会药源性疾病学委员会, 等. 中国精神科治疗药物监测临床应用专家共识(2022年版)[J]. 神经疾病与精神卫生, 2022, 22(8): 601-608. DOI: 10.3969/j.issn.1009-6574.2022.08.013.

9.Schoretsanitis G, Haen E, Gründer G, et al. Pharmacokinetic drug-drug interactions of mood stabilizers and risperidone in patients under combined treatment[J]. J Clin Psychopharmacol, 2016, 36(6): 554-561. DOI: 10.1097/JCP.0000000000000601.

10.Castberg I, Westin AA, Skogvoll E, et al. Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine[J]. Acta Psychiatr Scand, 2017, 136(5): 455-464. DOI: 10.1111/acps.12794.

11.丰丽莼, 杨博涵, 王雪芹, 等. UPLC-MS/MS法测定人血浆中奥氮平、利培酮和帕潘立酮的浓度[J]. 中国药房, 2017, 28(8): 1045-1048. [Feng LC, Yang BH, Wang XQ, et al. Simultaneous determination of olanzapine, risperidone and pali-peridone in human plasma by UPLC-MS/MS[J]. China Pharmacy, 2017, 28(8): 1045-1048.] DOI: 10.6039/j.issn.1001-0408.2017.08.10.

12.The World Health Organization. A healthy lifestyle—WHO recommendations 2010[EB/OL]. (2022-07-15) [2022-08-01]. https://www.who.int/europe/news-room/fact-sheets/item/a-healthy-lifestyle---who-recommendations.

13.周谢海, 夏清荣, 单锋, 等. 某三甲精神病院利培酮血药浓度监测现状及影响因素分析[J]. 中国医院药学杂志, 2021, 41(23): 2474-2477, 2499. [Zhou XH, Xia QR, Shan F, et al. Serum concentration monitoring and influen-tial factors analysis of risperidone in a grade A psychological hospital[J]. Chinese Journal of Hospital Pharmacy, 2021, 41(23): 2474-2477, 2499.] DOI: 10.13286/j.1001-5213.2021.23.16.

14.陈春武, 栾燕, 王曾晖, 等. 3种常见抗精神分裂药物的血药浓度分析[J]. 中国药物应用与监测, 2020, 17(6): 360-363. [Chen CW, Luan Y, Wang ZH, et al. Analysis on blood concentration of three common anti-psychotic drugs[J]. Chinese Journal of Drug Application and Monitoring, 2020, 17(6): 360-363.] DOI: 10.3969/j.issn.1672-8157.2020.06.002.

15.卢浩扬, 江晓佳, 尚德为, 等. 利培酮在精神分裂症患者中的血清药物浓度/剂量比影响因素研究[J]. 中国临床药理学杂志, 2018, 34(2): 117-119. [Lu HY, Jiang XJ, Shang DW, et al. Influential factors of serum concentra-tion/dosage ratio for schizophrenia patients after oral administration of risperidone[J]. Chinese Jour-nal of Clinical Pharmacology, 2018, 34(2): 117-119.] DOI: 10.13699/j.cnki.1001-6821.2018.02.007.

16.Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation[J]. Pharmacol Ther, 2013, 138(1): 103-141. DOI: 10.1016/j.pharmthera.2012.12.007.

17.Park PW, Seo YH, Ahn JY, et al. Effects of age and gender on the cytochrome P450 2D6 activity in a Korean population[J]. J Clin Pharm Ther, 2021, 46(6): 1659-1664. DOI: 10.1111/jcpt.13507.

18.Trenaman SC, Bowles SK, Andrew MK, et al. The role of sex, age and genetic polymorphisms of CYP enzymes on the pharmacokinetics of anticholinergic drugs[J]. Pharmacol Res Perspect, 2021, 9(3): e00775. DOI: 10.1002/prp2.775.

19.Kneller LA, Hempel G. Modelling age-related changes in the pharmacokinetics of risperidone and 9-hydroxyrisperidone in different CYP2D6 phenotypes using a physiologically based pharmacokinetic approach[J]. Pharm Res, 2020, 37(6): 110. DOI: 10.1007/s11095-020-02843-7.

20.Rojo LE, Gaspar PA, Silva H, et al. Metabolic syndrome and obesity among users of second generation antipsychotics: a global challenge for modern psychopharmacology[J]. Pharmacol Res, 2015, 101: 74-85. DOI: 10.1016/j.phrs.2015.07.022.

21.Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in hu-mans[J]. Clin Pharmacokinet, 2010, 49(2): 71-87. DOI: 10.2165/11318100-000000000-00000.

22.Paulzen M, Haen E, Stegmann B, et al. Body mass index (BMI) but not body weight is associated with changes in the metabolism of risperidone: a pharmacokinetics-based hypothesis[J]. Psychoneuroen-docrinology, 2016, 73: 9-15. DOI: 10.1016/j.psyneuen.2016.07.009.

23.Foucaud-Vignault M, Soayfane Z, Ménez C, et al. P-glycoprotein dysfunction contributes to hepatic steatosis and obesity in mice[J]. PLoS One, 2011, 6(9): e23614. DOI: 10.1371/journal.pone.0023614.

24.Bergiannaki JD, Kostaras P. Pharmacokinetic and pharmacodynamic effects of psychotropic medica-tions: differences between sexes[J]. Psychiatriki, 2016, 27(2): 118-126. DOI: 10.22365/jpsych.2016.272.118.

25.Islam MM, Iqbal U, Walther BA, et al. Gender-based personalized pharmacotherapy: a systematic re-view[J]. Arch Gynecol Obstet, 2017, 295(6): 1305-1317. DOI: 10.1007/s00404-017-4363-3.

26.Trenaman SC, Bowles SK, Andrew MK, et al. The role of sex, age and genetic polymorphisms of CYP enzymes on the pharmacokinetics of anticholinergic drugs[J]. Pharmacol Res Perspect, 2021, 9(3): e00775. DOI: 10.1002/prp2.775.

27.Okhuijsen-Pfeifer C, Huijsman EAH, Hasan A, et al. Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis[J]. Acta Psychiatr Scand, 2018, 138(4): 281-288. DOI: 10.1111/acps.12954.

28.Liu X, Sun H, Zhang Y, et al. Clozapine affects the pharmacokinetics of risperidone and inhibits its me-tabolism and P-glycoprotein-mediated transport in vivo and in vitro: a safety attention to antipsy-chotic polypharmacy with clozapine and risperidone[J]. Toxicol Appl Pharmacol, 2021, 422: 115560. DOI: 10.1016/j.taap.2021.115560.

29.郭涛, 左金梁, 夏东亚, 等. 中国汉族和回族药物代谢酶细胞色素P450(CYP)3A4、CYP2C9、CYP2C19及CYP2D6基因多态性分析[J]. 中国临床药理学杂志, 2012, 28(4): 281-284. [Guo T, Zuo JL, Xia DY, et al. Genetic polymor-phism analysis of cytochrome P450 (CYP)3A4, CYP2C9, CYP2C19 and CYP2D6 in Chinese Han and Hui pop-ulation[J]. Chinese Journal of Clinical Pharmacology, 2012, 28(4): 281-284.] DOI: 10.3969/j.issn.1001-6821.2012.04.013.