Aim To study the pharmacokinetics of po-lyethylene glycol conjugation on EILDVP peptide in mice by injection through tail vein.Methods KM mice,saturated thyroid gland with compound of NaI, were injected for 1 25 I labeled EILDVP-Tyr-NH2 ,EILD-VP-Cys (mPEG2000-MAL)-Tyr-NH2 and EILDVP-Cys (mPEG20000-MAL)-Tyr-NH2 peptides (1 25 I:5 mL · kg -1 volume 3.441 GBq·L -1 concentration)by tail intravenous,respectively.Blood samples at different time intervals were obtained,blood plasma was separa-ted,and the radioactivity of precipitation after trichloro-acetic acid (TCA)treatment was tested.According to standard curve equation, the plasma concentration curve and pharmocokinetic parameters were depicted by means of 3P97 pharmocokinetics software.Results Concentration range of 3.75 ~480 μg·L -1 of three 1 25 I labled peptides in plasma from mice had good line-ar relationship.Recovery of method was 88.92% ~ 1 06.66%,and RSD <1 0%.The half-life time (T1 /2 ) of EILDVP-Tyr-NH2 peptide modified by mPEG2000 and mPEG20000 ,labled by 1 25 I was 0.43h and 1 .94h,re-spectively,which was 1 .54 times and 6.93 times that of prototype peptide (T1 /2 =0.28h),and the clear-ances (Cl)were 1 .23 times and 24.71 times,respec-tively.The apparent distribution volume (V)values of the three species were small,which might mainly dis-tributed in the plasma.Conclusions Suitable for mo-lecular mass mPEG modified the EILDVP peptides could extend to maintain time in vivo,which could play a positive role in improving efficacy.In the experimen-tal range,EILDVP peptide modified by larger molecu-lar mass of mPEG20000 has better effect.%目的：探讨聚乙二醇修饰改善 EILDVP 肽体内过程的效果。方法KM小鼠以 NaI 饱和甲状腺后，按5 mL·kg －1容积，分别尾静脉注射3．441 GBq·L －1浓度的125 I 标记的EILDVP-Tyr-NH2、EILDVP-Cys （mPEG2000-MAL）-Tyr-NH2和EILDVP-Cys （mPEG20000-MAL）-Tyr-NH2肽。给药后不同时间取血，分离血浆，经三氯乙酸处理后测定沉淀部分放射性；测定数据分别代入已制备的相应标准曲线方程，取得血药浓度－时间数据，经3P97药动学统计软件计算主要药代动力学参数。结果在3.75～480μg·L －1浓度范围内，3种125 I标记肽线性关系良好，回收率在88.92％～106.66％之间，日内变异系数（RSD）＜10％；125 I 标记的 mPEG2000和 mPEG20000修饰 EILDVP-Tyr-NH2肽的血浆半衰期（T1／2）分别为0.43 h和1.94 h、较原型肽（0.28 h）延长1.54倍和6.93倍，清除率（Cl）分别降低1.23倍和24.71倍；3种受试化合物表观分布容积（V）值均较小，主要分布在血浆中。结论适宜分子质量 mPEG 修饰有利于延长 EILDVP 肽的体内维持时间，对提高药效具有积极意义；在实验范围内，分子质量较大的mPEG20000对 EILDVP 肽修饰效果较好。
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