McVey Elaine, Hirsch Laurence, Sutter Diane E, Kapitza Christoph, Dellweg Sibylle, Clair Janina, Rebrin Kerstin, Judge Kevin, Pettis Ronald J
BD Technologies, Research Triangle Park, North Carolina 27709, USA.
J Diabetes Sci Technol. 2012 Jul 1;6(4):743-54. doi: 10.1177/193229681200600403.
Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery.
The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject's optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl.
The primary end point, postprandial time in range (70-180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90-120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0-2 h, all p < .05).
This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.
皮内（ID）给药已被证明可加速胰岛素的药代动力学（PK）。我们比较了在每日两次标准化固体混合餐（早餐和午餐）前使用基于微针的皮内给药或传统皮下（SC）给药方式给予赖脯胰岛素后的PK和药效学（PD）效应。
本研究纳入22名1型糖尿病受试者，采用八臂完全交叉区组设计。其中一组确定每位受试者的最佳餐时剂量。在另外六组中，最佳剂量、较高剂量和较低剂量（+30%，-30%）分别以随机顺序进行皮内和皮下给药。最后一组评估皮内最佳剂量的更早给药时间（-12分钟与-2分钟）。餐后6小时收集PK/PD数据。全程给予静脉基础常规胰岛素，并将餐前血糖（BG）调整至115mg/dl。
主要终点，餐后血糖在目标范围内的时间（70-180mg/dl），在皮下和皮内给药的总体血糖控制水平较高的情况下，未显示出基于给药途径的差异。次要胰岛素PK终点显示，与皮下给药相比，皮内给药在不同剂量和餐次下的药物可用性更快（∆Tmax -16分钟，∆T50上升 -7分钟，∆T50下降-30分钟，均p <.05）。皮内给药Tmax的受试者内和受试者间变异性均显著更低。皮内给药在不同剂量和餐次下显示出适度的、具有统计学意义的次要PD差异，通常在餐后90-120分钟内（90分钟时∆12mg/dl BG，∆7mg/dl BGmax，0-2小时内∆7mg/dl平均BG，均p <.05）。
本研究表明，皮内胰岛素给药在全身可用性速度和PK一致性方面优于皮下给药，并且可能改善餐后血糖控制。
