重组甘精胰岛素注射液连续给药不同时间在犬体内的药动学研究

目的:研究重组甘精胰岛素注射液连续给药不同时间在犬体内的药动学。方法:采用125I胰岛素放射免疫分析药盒测定犬血中胰岛素水平。取犬随机分为高、中、低剂量(0·26、0·13、0·065mg·kg-1)组,每组6只,皮下注射相应重组甘精胰岛素,每日1次,连续给药12周,分别测定给药6、12周末各组犬血中胰岛素水平,并用3p97软件计算药动学参数。结果:胰岛素检测浓度线性范围为40～1280mU·L-1(r=0·9917),最低定量限为40mU·L-1,平均相对回收率为(96·34±4·91)%,RSD均<12·0%。犬血中重组甘精胰岛素的药动学参数分别为给药6周末的t1/2α:(0·89±0·40)～(1·43±1·01)h,cssmax:(2·30±1·16)～(11·69±4·26)mU·mL-1,AUC0～12h:(12·53±1·44)～(65·80±39·12)mU·h·mL-1;给药12周末的t1/2α:(0·68±0·48)～(1·18±0·83)h,cssmax:(1·92±0·79)～(8·62±1·51)mU·mL-1,AUC0～12h:(19·36±19·04)～(60·25±17·62)mU·h·mL-1,2时间点药动学参数比较无明显差异。结论:重组甘精胰岛素短时(给药6周)与长时(给药12周)给药的药动学参数未见明显差异。

Pharmacokinetics Study of Recombined Insulin Glargine in Dogs after Different Time of Consecutive Administration

OBJECTIVE:To study the pharmacokinetics of recombined insulin glargine in beagle dogs after different time of consecutive administration.METHODS:125I radio immunoassay kit was used to analyze the level of insulin in blood of beagle dogs.Beagle dogs were randomly divided into high-dose,medium-dose and low-dose groups(0.26,0.13,0.065 mg·kg-1) with 6 dogs in each group once a day for consecutive 12 weeks.The levels of insulin in blood sample were determined after 6 or 12 weeks of treatment and the pharmacokinetic parameters were calculated by 3p97 software.RESULTS:The linear range of glargine was 40～ 1 280 mU·L-1(r=0.991 7),the lowest limit of quantification was 40 mU·L-1.Average recovery rate was(96.34±4.91)%(RSD<12.0%).The pharmacokinetic parameters of recombined insulin glargine in beagle dogs after 6 weeks of treatment were as follows:t1/2α:(0.89±0.40)～(1.43±1.01) h;cssmax:(2.30±1.16)～(11.69±4.26) mU·mL-1;AUC0～12 h:(12.53±1.44)～(65.80±39.12) mU·h·mL-1.The pharmacokinetic parameters of recombined insulin glargine after 12 weeks of treatment were as follows:t1/2α:(0.68±0.48)～(1.18±0.83) h,cssmax:(1.92±0.79)～(8.62±1.51) mU·mL-1,AUC0～12 h:(19.36±19.04)～(60.25±17.62) mU·h·mL-1.There was no significant difference in pharmacokinetic parameters after 6 weeks and 12 weeks of treatment.CONCLUSION:The pharmacokinetic parameters of recombined insulin glargine have no significant difference after short-term(6 weeks) and long-term(12 weeks) treatment.