COMPARATIVE PHARMACOKINETICS AND GLUCODYNAMICS OF 2 HUMAN INSULIN MIXTURES
COMPARATIVE PHARMACOKINETICS AND GLUCODYNAMICS OF 2 HUMAN INSULIN MIXTURES
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DOI：
10.2337/diacare.17.5.366
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发表时间：
1994-05-01
期刊：
影响因子：
16.2
通讯作者：
CERIMELE, B
中科院分区：
文献类型：
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作者：
WOODWORTH, JR;HOWEY, DC;CERIMELE, B
目的-比较和对比两种胰岛素混合物的药代动力学和葡萄糖动力学，一种是50% NPH人胰岛素和50%常规人胰岛素（50/50），另一种是70% NPH人胰岛素和30%常规人胰岛素（70/30），研究设计和方法-我们给予50/50和70/50的单剂量，以随机交叉方式向18名志愿者提供10种胰岛素。所有受试者均接受0.3 U/kg的每种混合物，间隔至少7天。每次给药均在空腹过夜后和葡萄糖钳夹期间进行，以维持血糖正常状态。每次治疗后，我们通过频繁的血液采样来测量血清胰岛素和C肽浓度。根据C肽校正的胰岛素数据计算药代动力学测量值，包括最大胰岛素浓度（C-max）、达到最大胰岛素浓度的时间（t（max））、终末速率常数（β）、从0至无穷大的曲线下面积（AUC（0）（无穷大））和平均滞留时间（MRT）。根据C肽浓度（最小C肽浓度[C-min]、至最小C肽浓度的时间[t（min）]、C肽基线与C肽抑制曲线之间的面积[AOC（c）]、较基线的绝对最大差异[S-diff]和葡萄糖钳夹测量值）总结药效学测量值。葡萄糖钳夹测量包括来自葡萄糖输注速率（GIR）文件的最大输注速率（R（max））和至R（max）的时间（TR（max）），以及在研究期间在前4小时内输注的累积葡萄糖（（4）（0）G（tot））和输注的总葡萄糖（G（tot））。发现50/50混合物的胰岛素C-max和β值在统计学上更大，而70/30混合物具有更大的MRT。在葡萄糖动力学方面也检测到统计学差异，50/50混合物的R（max）和（4）（0）G（tot）值更大。值得注意的是，胰岛素AUC（0）（无穷大）和G（总）values.CONCLUSIONS -更高的胰岛素浓度和更大的初始反应，目前与50/50的混合物，但两种混合物具有等效的生物利用度和累积效应。这些结果支持在需要更好的初始血糖控制的情况下使用50/50混合物。
OBJECTIVE - To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg.RESEARCH DESIGN AND METHODS - We administered single doses of 50/50 and 70/10 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by al least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and C-peptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (C-max), time to maximum insulin concentration (t(max)), terminal rate constant (beta), area under the curve from 0 to infinity (AUC(0)(infinity)), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [C-min], time to minimum C-peptide concentration [t(min)], area between the C-peptide baseline and the C-peptide suppression curve [AOC(c)], absolute maximal difference from baseline [S-diff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (R(max)) and time to R(max) (TR(max)) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h ((4)(0)G(tot)) and total glucose infused (G(tot)) during the study.RESULTS - For the pharmacokinetic assessment, statistically greater values of insulin C-max and beta were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of R(max) and (4)(0)G(tot) found with the 50/50 mixture. Notably, differences were not detected for insulin AUC(0)(infinity) and G(tot) values.CONCLUSIONS - Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.