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

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

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。

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.