双氯芬酸钠对大鼠足跖肿胀的抑制作用及其与肿胀组织中药物浓度的关系

The inhibitory effect of diclofenac sodium on carrageenan rat paw oedema and the relationship with the drug concentration in the rat swelling paw tissue

目的：观察双氯芬酸钠对鹿角菜所致大鼠足跖肿胀的抑制作用及其与肿胀组织和血浆中药物浓度的关系。方法：足跖皮下注射１ ％ 鹿角菜制备大鼠足跖肿胀模型，观察双氯芬酸钠对足跖肿胀的抑制作用，并采用高效液相色谱法测定该模型中足跖肿胀组织和血浆中的双氯芬酸钠浓度，分析其药动学特征。结果：灌胃给予双氯芬酸钠（１０ ｍｇ·ｋｇ － １） 对足跖浮肿的抑制率为３２ ％ ～５７ ％ ；消除相中双氯芬酸在足跖肿胀组织中的浓度高于血浆，消除较血浆缓慢， Ｔ１／２ 分别为３ ．４ ｈ 和１ ．５ ｈ ，消除速率常数 Ｋ 分别为０ ．２０６ ５ 和０ ．４７３ ３ ，注射鹿角菜后的 Ａ Ｕ Ｃ０ ～ Ｔｎ 分别为９ ．４７５ ５ μｇ·ｍｌ－ １·ｈ 和１ ．８３ μｇ·ｍｌ－ １·ｈ 。结论：双氯芬酸钠对大鼠足跖肿胀抑制作用的延长效应与药物在肿胀组织中蓄积相关。

OBJECTIVE:To present the inhibitory effect of diclofenac sodium on carrageenan rat paw oedema and the relationship with the drug concentrations in the rat serum and swelling paw tissue.METHODS:After the rat was given a single oral dose of diclofenac sodium (10 mg·kg -1 ),the inhibitory effect of diclofenac soduim on carrageenan rat paw oedema was measured and the drug concentration in the rat serum and swelling paw tissue were determined by HPLC.RESULTS:The diclofenac sodium resulted in 32%～57% inhabitation of oedema formation.The concentration of diclofenac in rat serum was lower than that of the rat swelling hind paw tissue after injection of carrageenan.The pharmacokinetics parameters were as following: T 1/2 in the tissue and serum were 3.4 h and 1.5 h, K were 0.206 5 and 0.473 3 ,and AUC 0～Tn were 9.475 5 μg·ml -1 ·h and 1.83 μg·ml -1 ·h,respectively.CONCLUSIONS:The accumulation of diclofenac sodium in the inflammatory tissue may contribute to the prolonged therapeutic effect.