Effect of cutaneous blood flow on absorption of insulin: a methodological study in healthy male volunteers

Absorption of drugs from subcutaneous tissue depends on several factors, including tissue perfusion at the administration site. Tissue perfusion can be manipulated by e.g. application of local heat. This may subsequently alter the rate or amount of absorption of drugs from a subcutaneous depot. The aim of the present study was to investigate if increased tissue perfusion after controlled local heating can change the absorption of subcutaneously administered short-acting insulin (Actrapid®, 100IU/ml). Thirteen healthy Caucasian males participated in two randomized experimental sessions; one session with locally applied controlled heat at the injection site, and a control session without local heat application. Tissue perfusion (blood flow) was monitored with Laser Doppler Imaging, and blood samples were taken to assess the levels of glucose and insulin. Local heat application at the site of insulin injection significantly enhanced tissue perfusion by approximately 145%. However, no correlation was found between insulin absorption and tissue perfusion. Based on our findings, it was concluded that tissue perfusion is not the rate-limiting factor in the absorption of high-concentration short-acting insulin from a subcutaneous depot. It is suggested that dissociation of insulin hexamers into dimers and monomers is a major rate limiting factor to the absorption.