CYP2D6抑制剂对艾瑞昔布大鼠体内药代动力学的影响  

Effect of an Inhibitor of CYP2D6 on the Pharmacokinetic of Imrecoxib in Rats

作　　者：何文娟[1] 王伟美 贡莹[1] 张志清[1] HE Wenjuan;WANG Weimei;GONG Ying;ZHANG Zhiqing(The Second Hospital of Hebei Medical University,Shijiazhuang,Hebei,China 050000;Harrison International Peace Hospital,Hengshui,Hebei,China 053000)

机构地区：[1]河北医科大学第二医院,河北石家庄050000 [2]哈励逊国际和平医院,河北衡水053000

出　　处：《中国药业》2020年第7期71-74,共4页China Pharmaceuticals

基　　金：河北省自然科学基金资助项目[H2016206538]。

摘　　要：目的考察CYP2D6抑制剂帕罗西汀对艾瑞昔布在大鼠体内药代动力学的影响。方法选用甲苯磺丁脲为内标,色谱柱为Diamonsil C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-水-甲酸(85∶15∶0.1,V/V/V),等度洗脱,流速为1.0 mL/min,柱温为30℃。将40只健康雄性SD大鼠随机分为实验组和对照组,各20只,实验组大鼠灌胃帕罗西汀溶液2 mg/kg,对照组大鼠灌胃等量1‰羧甲基纤维素溶液,1次/日,连续给予7 d。两组大鼠均于第8天灌胃艾瑞昔布灌胃液(20 mg/kg),并按时取血,测定血药浓度,采用DAS 2.1.1软件拟合药-时曲线(AUC),并计算药代动力学参数,采用SPSS 13.0统计学软件分析。结果实验组的0-∞药时曲线下面积(AUC0-∞)为(1730.4±606.5)mg/(h·L)明显高于对照组的(1331.3±592.6)mg/(h·L)(P<0.05);实验组的峰浓度(Cmax)为(192.1±70.8)mg/L,明显高于对照组的(162.2±53.0)mg/L(P<0.05);实验组的清除率(CL)为(0.01±0.01)L/(kg·h),明显优于对照组的(0.02±0.01)L/(kg·h)(P<0.05)。结论CYP2D6抑制剂帕罗西汀预处理的大鼠,其体内艾瑞昔布的暴露量增大,清除率减小。CYP2D6抑制剂减慢了艾瑞昔布在大鼠体内的代谢,推断CYP2D6参与了艾瑞昔布的代谢。Objective To study the effect of CYP2D6 on the pharmacokinetic of imrecoxib in rats.Methods Tolbutamide was selected as the internal standard.The samples were separated on a chromatographic column of Diamonsil C18(150 mm×4.6 mm,5μm)and a mobile phase consisting of acetonitrile-water-formic acid(85∶15∶0.1,V/V/V)was used at a flow rate of 1.0 mL/min and a column temperature of 30℃.Forty healthy male SD rats were randomly divided into the test group and control group,20 in each group.The test group were pretreated with paroxetine(2 mg/kg)and the control group with the same dosage of 1‰carboxymethylcellulose,once a day,for consecutive 7 days,respectively.On day 8,imrecoxib was administered orally at a dose of 20 mg/kg to all rats.Blood samples from plexus venous at fundus oculi were collected and detected.The Area Under Curve(AUC)and pharmacokinetics were calculated with DAS 2.1.1 software and analyzed with SPSS 13.0 software.Results AUC0-∞of imrecoxib in the test group was(1730.4±606.5)mg/(h·L),which was significantly higher than(1331.3±592.6)mg/(h·L)in the control group(P<0.05).Cmax in the test group was(192.1±70.8)mg/L,which was significantly higher than(162.2±53.0)mg/L in the control group(P<0.05).Clearance rate(CL)in the test group was(0.01±0.01)L/(kg·h),which was significantly higher than(0.02±0.01)L/(kg·h)in the control group(P<0.05).Conclusion The metabolism of imrecoxib is slowed down in rats pretreated with paroxetine with increased exposure and decreased clearance.We infer that CYP2D6 is involved in the metabolism of imrecoxib.

关 键 词：艾瑞昔布 CYP2D6 药代动力学 帕罗西汀 

分 类 号：R965[医药卫生—药理学] R977.3[医药卫生—药学]