甲泼尼龙片对泊沙康唑口服混悬液在大鼠体内的药代动力学影响  

Effect of methylprednisolone on the pharmacokinetics of posaconazole oral suspension in rats

作　　者：许萌[1] 袁叶[1] 李德强[1] 杨秀岭[1] XU Meng;YUAN Ye;LI De-qiang;YANG Xiu-ling(Department of Pharmacy,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学第二医院药学部,河北石家庄050000

出　　处：《中国临床药理学杂志》2022年第11期1247-1250,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省医学科学研究重点课题基金资助项目(20200062)。

摘　　要：目的考察甲泼尼龙片对泊沙康唑口服混悬液在大鼠体内药代动力学的影响。方法将大鼠随机分为实验组和对照组,每组5只。实验组灌胃给予3.6 mg·kg^(-1)甲泼尼龙灌胃液,qd,连续7 d;对照组灌胃给予等量纯化水,qd,连续7 d。第8天,2组大鼠分别给予甲泼尼龙或纯化水后,立即灌胃给予20 mg·kg^(-1)泊沙康唑口服混悬液。于给药后不同时间点眼内眦取血,用HPLC法测定泊沙康唑血药浓度,用DAS 2.1.1软件拟合药代动力学参数。结果实验组和对照组的AUC_(0-t)分别为(12.20±4.16)和(22.63±4.33)μg·mL^(-1)·h,AUC_(0-∞)分别为(24.80±6.62)和(27.25±4.75)μg·mL^(-1)·h,t_(1/2)分别为(21.91±4.32)和(13.30±2.21)h,C_(max)分别为(0.84±0.15)和(1.21±0.09)μg·mL^(-1),表观分布容积(V_(d))分别为(21.25±4.18)和(13.89±3.21)L·kg^(-1),清除率(CL)分别为(0.84±0.25)和(0.75±0.12)L·h^(-1)·kg^(-1)。实验组的AUC_(0-t)、C_(max)和V_(d)与对照组比较,差异均有统计学意义(均P<0.05)。结论合用甲泼尼龙后,泊沙康唑的AUC_(0-t)和C_(max)均显著降低,V_(d)明显增加,这说明甲泼尼龙对泊沙康唑口服混悬液在大鼠体内的药代动力学有一定影响。Objective To study the influence of methylprednisolone on the pharmacokinetic of posaconazole oral suspension in rats.Methods Rats were randomly divided into experimental group and control group with 5 rats in each group.Each rat in experimental group was given 3.6 mg·kg^(-1) of methylprednisolone intragastrically and each rat in control group was given equal volume of distilled water,once a day for 7 days.On day 8,after the rats were given methylprednisolone or purified water,each rat received a single dose of posaconazole oral suspension(20 mg·kg^(-1)) intragastrically.The blood samples were collected from epicanthal folds at different time after medication.The concentration of posaconazole was determined by HPLC.Then the pharmacokinetic parameters of posaconazole in each group were calculated by using DAS 2.1.1 software.Results The main pharmacokinetic parameters of control and experimental groups were obtained as follows:AUC_(0-t) were(22.63±4.33)and(12.20±4.16)μg·mL^(-1)·h,AUC_(0-∞)were(27.25±4.75)and(24.80±6.62)μg·mL^(-1)·h,t_(1/2) were(13.30±2.21)and(21.91±4.32)h,C_(max)were(1.21±0.09)and(0.84±0.15)μg·mL^(-1),V_(d) were(13.89±3.21)and(21.25±4.18)L·kg^(-1),CL were(0.75±0.12)and(0.84±0.25)L·h^(-1)·kg^(-1).Compared with the control group,the AUC_(0-t),C_(max) and V_(d) of the experimental group were significantly different(all P<0.05).Conclusion After the combination use of methylprednisolone,the AUC_(0-t) and C_(max) of posaconazole was significantly reduced,and Vd was significantly increased.The results of the pharmacokinetic experiments showed that the methylprednisolone has a certain effect on the pharmacokineitics of posaconazole in the rats.

关 键 词：甲泼尼龙 泊沙康唑 药代动力学 HPLC 大鼠 

分 类 号：R978.5[医药卫生—药品]