Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection
Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection
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DOI：
10.2337/dc15-0801
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发表时间：
2015-12-01
期刊：
影响因子：
16.2
通讯作者：
Fanelli, Carmine G.
中科院分区：
文献类型：
--
作者：
Lucidi, Paola;Porcellati, Francesca;Fanelli, Carmine G.
目的：晶体NPH胰岛素为两相溶液，可与溶剂或速效胰岛素（预混制剂）混合，注射前需要充分混合以完全重悬浮。本研究的目的是建立适当重悬与非重悬NPH胰岛素注射后的药代动力学（PK）和药效学（PD）。研究设计与方法在稳定状态下皮下注射NPH胰岛素0.35单位/kg后，通过笔重悬（R+，胰岛素笔倾斜20次）或非笔重悬（笔保持固定位置水平[R-水平]或垂直向上[R-上]或向下[R-下]）评估spk和PD。采用随机交叉设计，研究了11例1型糖尿病患者（年龄31.5 ~ 12岁，糖尿病病程17.5 ~ 7.7年，BMI 22.9 +/- 1.5 kg/m(2), A1C 7.2 +/- 0.4% [55.2 +/- 4.4 mmol/mol]）。结果与重悬NPH胰岛素（R+）相比，非重悬NPH胰岛素导致血浆胰岛素浓度[FIRI_AUC（0-研究结束）)（0-研究结束时浓度-时间曲线下的游离免疫反应胰岛素面积）]和PD活性[葡萄糖输注速率（GIR）_AUC（0-研究结束）]降低（R-水平和R-上升）或增加（R-下降）（P < 0.05）， PK/PD差异显著。与R+ (11.8 +/- 2.6 h)相比，NPH胰岛素作用时间R-上短（9.4 +/- 1.7 h）， R-下长（15.4 +/- 2.3 h） （P < 0.05）。PK [FIRI_AUC((0-end of study))]和PD [GIR_AUC((0-end of study))]的受试者内变异性（百分比变异系数）分别高达23%和62%。结论与重悬NPH胰岛素相比，缺乏重悬可显著改变PK/PD，并可能对1型糖尿病的日常血糖变异性有重要影响。
OBJECTIVECrystalline NPH insulin comes in a two-phase solution with either a solvent or a rapid-acting insulin (in premixed formulations) and needs adequate mixing for complete resuspension before injection. The aim of this study was to establish pharmacokinetics (PK) and pharmacodynamics (PD) after injection of appropriately resuspended versus nonresuspended NPH insulin.RESEARCH DESIGN AND METHODSPK and PD were assessed after subcutaneous injection of NPH insulin 0.35 units/kg at steady state by pen either resuspended (R+, tipping of insulin pen 20 times) or nonresuspended (pen maintained in fixed position either horizontally [R- horizontal] or vertically with tip up [R- up] or tip down [R- down]). Eleven subjects with type 1 diabetes (age 31.5 12 years, diabetes duration 17.5 7.7 years, BMI 22.9 +/- 1.5 kg/m(2), A1C 7.2 +/- 0.4% [55.2 +/- 4.4 mmol/mol]) were studied (euglycemic clamp) with a randomized crossover design.RESULTSCompared with resuspended NPH insulin (R+), nonresuspended NPH insulin resulted in profound PK/PD differences with either reduced (R- horizontal and R- up) or increased (R- down) plasma insulin concentrations [FIRI_AUC((0-end of study)) (free immunoreactive insulin area under the concentration-time curve between 0 and end of study)] and PD activity [glucose infusion rate (GIR)_AUC((0-end of study))] (all P < 0.05). Duration of NPH insulin action was shorter in R- up (9.4 +/- 1.7 h) but longer in R- down (15.4 +/- 2.3 h) compared with R+ (11.8 +/- 2.6 h) (P < 0.05). Within-subject variability (percent coefficient of variation) among studies was as high as 23% for PK [FIRI_AUC((0-end of study))] and 62% for PD [GIR_AUC((0-end of study))].CONCLUSIONSCompared with resuspended NPH insulin, lack of resuspension profoundly alters PK/PD and may importantly contribute to day-to-day glycemic variability of type 1 diabetes.