Absorption kinetics of insulin after subcutaneous administration

• Published in: European journal of pharmaceutical sciences Vol. 36; no. 1; pp. 78 - 90
• Main Authors: Søeborg, Tue, Rasmussen, Christian Hove, Mosekilde, Erik, Colding-Jørgensen, Morten
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kindlington Elsevier B.V 31.01.2009; Elsevier
• Subjects: Adsorption; Animals; Biological and medical sciences; Crystal parameter effect; Crystallization; Diffusion; Dose size effect; General pharmacology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Injections, Subcutaneous; Insulin - administration & dosage; Insulin - chemistry; Insulin - pharmacokinetics; Insulin absorption; Insulin concentration effect; Medical sciences; NPH insulin; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Soluble insulin; Soluble insulin; Dose size effect; Insulin absorption; NPH insulin; Insulin concentration effect; Crystal parameter effect; Pancreatic hormone; Pharmaceutical technology; Neutral insulin injection; Insulin; Hypoglycemic agent; Absorption; Concentration effect; Subcutaneous administration; Kinetics; Pharmacokinetics; Isophane insulin
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2008.10.018

Many diabetic patients depend on regular and well-controlled administration of insulin to avoid unacceptable excursions in plasma glucose. A complicating factor is that the absorption of insulin shows a considerable variability, both between patients, and from administration to administration for the same patient. To understand the mechanisms that influence this variability we present a quantitative description of the absorption kinetics for both soluble insulin and insulin crystals. The concentration dependent distribution of insulin between different oligomers is first analysed and described. Next, the disappearance of soluble and crystalline insulin from subcutis is described and explained as a function of the administered dose, the insulin concentration and crystal specific parameters, but without diffusion. The effect of diffusion is then included, and the appearance of insulin in plasma following subcutaneous administration is simulated and discussed. Our results not only explain the observed variability, but they also explain how dose size, insulin concentration, insulin crystals etc. influence the absorption kinetics.