Plasma concentration of 125 I labeled and polyethylene glycol conjugation to EILDVP peptide in mice / 中国药理学通报

ABSTRACT

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.