CAJ | 학술논문

目的：评价国产与国外已上市的重组人胰岛素注射液在Beagle犬体内的药代动力学及生物等效性。方法用两制剂、双周期、自身对照随机交叉单剂量实验设计。12只健康Beagle犬分为实验组（试验药）和对照组（对照药），每组5只，皮下注射重组人胰岛素5 U，不同时间经静脉采集血浆，测定动物血糖水平；放射免疫分析（ RIA）法检测血药浓度；用DAS 2.0软件拟合计算药代动力学参数，并进行生物等效性分析。结果实验组和对照组胰岛素主要药代动力学参数：t1／2为（1.06±0.17），（1.06±0.35） h；Cmax 为（97.10±45.20），（91.30±28.20）μU· mL-1；tmax为（0.49±0.19），（0.49±0.18） h；AUC0-t为（168.00±40.50），（168.00±41.90）μU · mL-1· h。血浆最低葡萄糖浓度（Cmin）分别为（1.36±0.28），（1.37±0.34） mmol· L-1，最低浓度所需时间（tmin）分别为（1.57±0.55），（1.74±0.65） h。 Cmax和 AUC0-t[1-2α]置信区间分别为85.5％~117.7％和97.0％~103.3％。结论2种重组人胰岛素注射剂在健康Beagle 犬体内具有生物等效性。
목적：평개국산여국외이상시적중조인이도소주사액재Beagle견체내적약대동역학급생물등효성。방법용량제제、쌍주기、자신대조수궤교차단제량실험설계。12지건강Beagle견분위실험조（시험약）화대조조（대조약），매조5지，피하주사중조인이도소5 U，불동시간경정맥채집혈장，측정동물혈당수평；방사면역분석（ RIA）법검측혈약농도；용DAS 2.0연건의합계산약대동역학삼수，병진행생물등효성분석。결과실험조화대조조이도소주요약대동역학삼수：t1／2위（1.06±0.17），（1.06±0.35） h；Cmax 위（97.10±45.20），（91.30±28.20）μU· mL-1；tmax위（0.49±0.19），（0.49±0.18） h；AUC0-t위（168.00±40.50），（168.00±41.90）μU · mL-1· h。혈장최저포도당농도（Cmin）분별위（1.36±0.28），（1.37±0.34） mmol· L-1，최저농도소수시간（tmin）분별위（1.57±0.55），（1.74±0.65） h。 Cmax화 AUC0-t[1-2α]치신구간분별위85.5％~117.7％화97.0％~103.3％。결론2충중조인이도소주사제재건강Beagle 견체내구유생물등효성。
Objective To investigate the pharmacokinetic and bio-equivalence of domestic and imported recombinant human insulin injec-tion in Beagle dogs.Methods Twelve Beagle dogs were assigned into two groups and the two groups were separately singlely given with test preparation and reference preparation in the same dose in sc injection method according to a randomized two -phase crossover .The plasmas were sampled at different time points after subcutaneous administration and the blood glucose levels were determined by Roche Glucose meter synchronously.The radioimmunoassay ( RIA) method was used to deter-mine the concentration of blood insulin at the different sample points . The pharmacokinetic parameters were calculated by DAS 2.0 software. Results The main pharmacokinetics parameters of test preparation and reference preparation were as follows: t1/2 were ( 1.06 ±0.17 ) and (1.06 ±0.35 ) h; Cmax were ( 97.10 ±45.20 ) and ( 91.30 ±28.20 )μU· mL-1; tmax were ( 0.49 ±0.19 ) and ( 0.49 ±0.18 ) h; area AUC0-t were (168.00 ±40.50) and (168.00 ±41.90) μU· mL-1 · h, respectively. What′s more, Cmin of the test and the referenc were (1.36 ±0.28 ) and (1.37 ±0.34 ) mmol· L-1 separately, and the tmin were ( 1.57 ±0.55 ) and ( 1.74 ±0.65 ) h, respectively. The confidence intervals of Cmax and AUC0-t are 85.5% -117.7% and 97.0%-103.3%.Conclusion The results showed that the test and the reference preparation meet the regulatory cri-teria for the pharmacokinetic equivalence .