Time-action profile of an oral enteric insulin formulation in healthy Chinese volunteers

Clin Ther. 2012 Dec;34(12):2333-8. doi: 10.1016/j.clinthera.2012.11.004. Epub 2012 Nov 27.

Abstract

Background: Insulin is an essential treatment for both type 1 and 2 diabetes. Among the available routes of insulin administration, oral delivery is the most appealing option.

Objective: The purpose of this study was to evaluate the pharmacodynamic and pharmacokinetic profiles of orally administered enteric insulin and compare the time-action of these oral insulin capsules with neutral protamine Hagedorn (NPH) insulin.

Methods: This was a single-center, randomized, 4-period, crossover study. Twelve healthy volunteers (3 per group) received 1 of 3 doses of oral enteric insulin (50, 100, or 200 U) or 1 subcutaneous injection of NPH insulin (6 U) on 4 separate days. After administration, glucose infusion rates and serum insulin concentrations were monitored for 10 hours.

Results: Glucose infusion rates increased after administration of either NPH or oral enteric insulin. The mean times for maximal metabolic effects for 50, 100, and 200 U of oral enteric insulin were 250 (118), 170 (58), and 236 (132) minutes, respectively, compared with 243 (79) minutes for NPH insulin. The onset of action was slower for oral enteric insulin at 50 U (38 [10] minutes), 100 U (41 [18] minutes), and 200 U (65 [58] minutes) compared with NPH insulin (35 [8] minutes). The maximum glucose infusion rates for oral enteric insulin treatment (1.66 [0.50], 1.61 [1.00], and 1.80 [0.60] mg/kg/min for 50, 100, and 200 U, respectively) were lower compared with NPH insulin (2.06 [0.82] mg/kg/min), although these differences were not statistically significant.

Conclusions: Oral enteric insulin capsules induced significant glucodynamic effects and exhibited a time-action profile similar to that of NPH insulin in these healthy volunteers. No detectable increases in serum insulin concentration were observed in any treatment group. Trial registry number: ChiCTR-TRC-12001872.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Glucose / drug effects*
  • Capsules
  • China
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Injections, Subcutaneous
  • Insulin / administration & dosage*
  • Insulin / pharmacokinetics
  • Insulin / pharmacology
  • Insulin, Isophane / administration & dosage*
  • Insulin, Isophane / pharmacokinetics
  • Insulin, Isophane / pharmacology
  • Time Factors
  • Young Adult

Substances

  • Blood Glucose
  • Capsules
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Isophane