帕瑞昔布钠鼻用温敏凝胶在大鼠体内的药代动力学研究  

Pharmacokinetics of parecoxib sodium thermosensitive nasal gel in rats

作　　者：黄晶 李爽 吴春芝[2] 谷福根[2] HUANG Jing;LI Shuang;WU Chun-zhi;GU Fu-gen(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,Inner Mongolia,China;Affiliated Hospital of Inner Mongolia Medkal University,Hohhot 010050,Inner Mongolia,China)

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010110 [2]内蒙古医科大学附属医院内蒙古呼,内蒙古呼和浩特010050

出　　处：《中国临床药理学杂志》2022年第9期984-988,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究帕瑞昔布钠(PCX)鼻用温敏凝胶在大鼠体内的药代动力学。方法用HPLC法测定大鼠血中帕瑞昔布钠的浓度。色谱柱为InertSustain C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-水-磷酸(63∶37∶0.01),检测波长为240 nm,内标为布洛芬。按体质量将大鼠随机分为实验组和对照组,每组10只。对照组肌内注射0.5%帕瑞昔布钠溶液,实验组鼻腔给予帕瑞昔布钠鼻用温敏凝胶,剂量均为5.0 mg·kg^(-1)。计算主要药代动力学参数。结果帕瑞昔布钠在大鼠体内的药代动力学过程符合一室模型。实验组与对照组的药代动力学参数t_(max)分别为(0.10±0.04)和(0.15±0.04)h,C_(max)分别为(14.86±1.85)和(10.80±1.46)μg·mL^(-1),K_(a)分别为(21.18±4.75)/h和(10.96±3.06)/h,AUC_(0-t)分别为(10.22±2.36)和(4.09±0.72)μg·h·mL^(-1),AUC_(0-∞)分别为(10.65±2.74)和(4.41±0.83)μg·h·mL^(-1)。实验组与对照组比较,t_(max)明显减小,C_(max)、K_(a)、AUC_(0-t)及AUC_(0-∞)均明显增大,差异均有统计学意义(P<0.05或P<0.01)。帕瑞昔布钠鼻用温敏凝胶的相对生物利用度(F_(r))为241.50%。结论帕瑞昔布钠鼻用温敏凝胶在体内吸收快、生物利用度高、给药方便,有望成为上市帕瑞昔布钠注射剂的理想替代给药剂型。Objective To study the pharmacokinetics of parecoxib sodium(PCX)thermosensitive nasal gel in rats.Methods The concentrations of PCX in rat plasma were determined by high performance liquid chromatography.The chromatographic analysis was performed on an InertSustain C_(18) reversed phase column(250 mm×4.6 mm,5μm).The mobile phase consisted of acetonitrile,water and phosphoric acid(63∶37∶0.01)and detection wavelength was set at 240 nm.Ibuprofen was used as internal standard.Rats were randomly divided into test group and control group with 10 rats each group.PCX thermosensitive nasal gel was nasally administered to the test group and 0.5%PCX solution was given intramuscularly to the control group,the dose for each group was 5.0 mg·kg-1.The main pharmacokinetic parameters of PCX for the two groups were calculated by PKSolver 2.0 pharmacokinetic software.Results The pharmacokinetic process of PCX in rats after intramuscular and nasal administration both conformed to one-compartment model.The main pharmacokinetic parameters of PCX for test group and control group tmax were(0.10±0.04)and(0.15±0.04)h,C_(max) were(14.86±1.85)and(10.80±1.47)μg·mL^(-1),Kawere(21.18±4.75)and(10.96±3.06)h^(-1),AUC0-twere(10.22±2.36)and(4.09±0.72)μg·h·mL^(-1),AUC_(0-∞)were(10.65±2.74)and(4.41±0.83)μg·h·mL-1,respectively.Compared with control group,t_(max)for test group was obviously reduced,however,C_(max),Ka,AUC^(0-t)and AUC_(0-∞)for test group were all evidently increased.There was statistically significant difference in the above pharmacokinetic parameters between test and control groups(P<0.01).The relative bioavailability(Fr)of the PCX thermosensitive nasal gel was found to be 241.50%.Conclusion PCX thermosensitive nasal gel is expected to be an ideal alternative to the marketed PCX injection due to its rapid in vivo absorption,higher bioavailability,convenient administration.

关 键 词：帕瑞昔布钠 鼻用温敏凝胶 高效液相色谱 药代动力学 

分 类 号：R97[医药卫生—药品]