模拟热带海岛环境对炎性疼痛大鼠口服塞来昔布疗效的影响  

The impact of simulated tropical island environment on the pharmacokinetic characteristics and therapeutic effect of oral celecoxib in rat models of inflammatory pain

作　　者：林徐苗 刘洪桥 王童 孙莉 游嘉 杨涛 白玉树 马宇 熊源长 LIN Xu-miao;LIU Hong-qiao;WANG Tong;SUN Li;YOU Jia;YANG Tao;BAI Yu-shu;MA Yu;XIONG Yuan-chang(Department of Pain,Changhai Hospital,Naval Medical University,Shanghai 200433,China;Department of Spine Surgery,Changhai Hospital,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学第一附属医院疼痛治疗科,上海200433 [2]海军军医大学第一附属医院脊柱外科,上海200433

出　　处：《中国疼痛医学杂志》2024年第12期919-927,共9页Chinese Journal of Pain Medicine

基　　金：上海市创新医疗器械应用示范项目(23SHS04700);“深蓝123”军事医学研究专项(2019YSL008)。

摘　　要：目的:探讨模拟热带海岛环境对炎性疼痛大鼠口服塞来昔布(celecoxib, CXB)药代动力学和疗效的影响。方法:66只雄性SD大鼠随机分为模拟海岛环境组和对照组,分别在相应环境中饲养3天。36只大鼠口服CXB后测定血清药物浓度;30只大鼠构建炎性疼痛模型并测定痛阈。结果:模拟海岛环境改变了CXB的药代动力学特征,在中高剂量下,模拟海岛环境组大鼠的末端消除半衰期(t1/2)降低,AUC (0-t)和AUC (0-∞)显著低于对照组,而清除率显著高于对照组;痛阈检测显示,模拟海岛环境组炎性疼痛大鼠在注射CXB后3~5天的痛阈显著低于对照组;模拟海岛环境增加了大鼠肝脏CXB代谢关键酶CYP2C9的表达,并导致血清炎症因子升高。结论:模拟热带海岛环境可加快CXB的代谢速度,降低其抗炎镇痛效果。Objective:To investigate the effects of a simulated tropical island environment on the pharmacokinetics and efficacy of orally administered celecoxib(CXB)in inflammatory pain rats.Methods:Sixty-six male SD rats were randomly divided into a simulated tropical island environment group(STIE group)and a control group and were housed in their respective environment for three days.Serum drug concentrations were determined after oral administration of CXB in 36 rats,while 30 rats were used to establish an inflammatory pain model,and pain thresholds were measured.Results:The simulated island environment altered the pharmacokinetic characteristics of CXB,specifically,in the STIE group at medium to high doses,the terminal elimination half-life(t1/2)was reduced,and the area under the curve(AUC)values AUC(0-t)and AUC(0-∞)were significantly lower than those of the control group,while the clearance rate(CL)was significantly higher.Pain threshold assessments indicated that the pain thresholds of the inflammatory pain rats in the STIE group were significantly lower than those of the control group on days 3 to 5 post-CXB injection.Furthermore,the simulated island environment increased the expression of the key metabolic enzyme CYP2C9 in liver and led to elevated serum inflammatory factors.Conclusion:The simulated tropical island environment accelerated the metabolic rate of CXB and diminished its anti-inflammatory and analgesic effects.

关 键 词：热带海岛环境 高温高湿 塞来昔布 药代动力学 痛阈 炎症因子 大鼠 

分 类 号：R965[医药卫生—药理学]