辣椒素对大鼠体内氯氮平药代动力学的影响研究  

Study of capsaicin effects on clozapine pharmacokinetics in rats

作　　者：何佩华 胡礼军[1] 陈雨晴[1] 王占璋[1] 尚德为[1] 卢浩扬[1] 倪晓佳[1] 温预关[1] HE Pei - hua;HU Li - jun;CHEN Yu - qing;WANG Zhan - zhang;SHANG De - wei;LU Hao - yang;NI Xiao - jia;WEN Yu - guan(Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University / Guangzhou Huiai Hospital, Guangzhou 510370, Guangdong Province, China;Department of Phanrmey, The Third People＇ s Hosptial of Jiangmen, Jiangmen 529000, Guangdong Province, China)

机构地区：[1]广州医科大学附属脑科医院/广州市惠爱医院药学部,广州510370 [2]江门市第三人民医院药剂科,广东江门529000

出　　处：《中国临床药理学杂志》2018年第12期1424-1427,共4页The Chinese Journal of Clinical Pharmacology

基　　金：广州市医学重点学科建设基金资助项目(2017-2019)

摘　　要：目的研究在大鼠体内辣椒素对氯氮平及其代谢物的血药浓度及药代动力学的影响。方法按自身对照方法设计。对照组予以单剂量31.5 mg·kg^(-1)氯氮平,灌胃;经过5 d的清洗期后,实验组将对照组大鼠连续灌胃8 mg·kg^(-1)辣椒素7 d,于第8天灌胃辣椒素(8 mg·kg^(-1))与氯氮平(31.5 mg·kg^(-1))混悬液。分别于不同时间点采集血样,并用HPLC-MS/MS法检测氯氮平和去甲氯氮平的血药浓度,用DAS 3.2.4软件计算药代动力学参数。结果对照组和实验组中氯氮平的主要药代动力学参数如下:C_(max)分别为(323.59±97.03)和(560.49±208.53)μg·L^(-1),t_(max)分别为(0.95±0.35)和(0.85±0.27)h,t_(1/2)分别为(2.13±0.63)和(2.34±0.95)h,AUC_(0-∞)分别为(1769.71±780.02)和(2110.97±1109.88)μg·L^(-1)·h。结论辣椒素与氯氮平同用时可能会发生药物间相互作用,原因可能是辣椒素会增加氯氮平及其代谢物在大鼠体内的吸收,且抑制氯氮平的消除,因此,临床使用时应注意其潜在影响。Objective To study the effects of capsaicin on plasma concentration and pharmacokinetics of clozapine and its metabolites in rats.Methods Ten male Sprague-Dawley（ SD） rats were selected and the self control method was adopted. The control group was given a single dose of clozapine（ 31. 5 mg·kg^-1）. In the experimental group,rats in the control group after a 5 days period of cleaning were given the capsaicin（ 8 mg·kg^-1） for 7 days continuously,and were given the mixed suspension of capsaicin（ 8 mg·kg^-1） and clozapine（ 31. 5 mg·kg^-1 in the 8 th day. Blood samples were collected at different time points and detected the blood concentration of clozapine and N-desmethyl clozapine by HPLC-MS/MS. Finally, the pharmacokinetic parameters were calculated and statistical analyzed through DAS 3. 2. 4 software. Results The main pharmacokinetic parameters of clozapine in the control and test group were following： Cmaxwere（ 323. 59 ± 97. 03） and（ 560. 49 ± 208. 53） μg · L^-1; tmaxwere（ 0. 95 ± 0. 35） and（ 0. 85 ± 0. 27） h; t1/2 were（ 2. 13 ± 0. 63） and（ 2. 34 ± 0. 95） h;AUC0-∞were（ 1769. 71 ± 780. 02） and（ 2110. 97 ± 1109. 88）μg·L^-1·h^-1,respectively. Conclusion Capsaicin can inhibit the metabolism of clozapine in rats. Capsaicin and clozapine may interact with the main metabo-lic enzymes of clozapine.

关 键 词：辣椒素 氯氮平 去甲氯氮平 药代动力学 细胞色素P450 1A2 

分 类 号：R971[医药卫生—药品]