Stote Robert, Miller Michael, Marbury Thomas, Shi Leon, Strange Poul
CPEX Pharmaceuticals, Inc., Exeter, NH 03833, USA.
J Diabetes Sci Technol. 2011 Jan 1;5(1):113-9. doi: 10.1177/193229681100500116.
This pharmacokinetic (PK) study was designed to investigate the maximum intranasal insulin dose that could be achieved by repeated doses in a single nostril of a nasal spray of recombinant regular human insulin 1% in combination with cyclopentadecalactone (CPE-215) 2%, a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals, Inc.).
A nine-period crossover study of 8 healthy, nonsmoking subjects (ages 18-50, body mass index <33 kg/m², weight >70 kg) were studied. In a fasted state, subjects were randomly given 25, 50, and 75 U in a single nostril on the first day and randomly given 50, 75, and 100 U doses utilizing both nostrils on two subsequent days. After a 45-minute PK assessment, subjects were given a meal. To determine the mechanism of enhanced absorption in a single nostril, a second study utilizing 24 subjects under similar conditions received 25 U, placebo (P) that included CPE-215 plus 25 U, and 50 U in a single nostril.
Single nostril administration revealed enhanced absorption with maximum concentrations (C(max)) of 13, 65, and 96 µU/ml for the 25, 50, and 75 U doses, respectively. Dual nostril administration in two cohorts resulted in C(max) of 31/42, 65/52, and 88/79 µU/ml for the 50, 75, and 100 U, respectively. In the second cohort, C(max) was 23, 19, 56 µU/ml for the 25, P + 25, and 50 U doses, respectively.
Repeated dosing in a single nostril resulted in enhanced absorption; this was not due to the increased CPE-215 but to the increased insulin administered.
本药代动力学（PK）研究旨在探究通过在重组常规人胰岛素1%与环十五内酯（CPE - 215）2%（一种可增强分子跨粘膜吸收的化合物）组成的鼻喷雾剂的单个鼻孔中重复给药所能达到的最大鼻内胰岛素剂量（Nasulin™，CPEX制药公司）。
对8名健康、不吸烟的受试者（年龄18 - 50岁，体重指数<33 kg/m²，体重>70 kg）进行了为期九个周期的交叉研究。在禁食状态下，受试者第一天在单个鼻孔中随机给予25、50和75单位，随后两天在两个鼻孔中随机给予50、75和100单位剂量。经过45分钟的药代动力学评估后，给受试者提供一顿餐食。为确定单个鼻孔中吸收增强的机制，第二项在类似条件下对24名受试者进行的研究在单个鼻孔中给予25单位、包含CPE - 215加25单位的安慰剂（P）以及50单位。
单鼻孔给药显示吸收增强，25、50和75单位剂量的最大浓度（C(max)）分别为13、65和96 μU/ml。两个队列的双鼻孔给药中，50、75和100单位剂量的C(max)分别为31/42、65/52和88/79 μU/ml。在第二个队列中，25、P + 25和50单位剂量的C(max)分别为23、19和56 μU/ml。
在单个鼻孔中重复给药导致吸收增强；这并非由于CPE - 215增加，而是由于胰岛素给药量增加。
