Subcutaneous Absorption of U-40 and U-100 Insulin

Abstract

Single strength insulin has been recommended in order to reduce dosage errors (Bloom, Keen and Watkins 1981). Most of Europe uses insulin of 40 units/ml (U-40) only, whereas the United States, Canada, Australia, and, recently, Britain have adopted a sole insulin strength of 100 units/ml (U-100). We studied the absorption of identical doses of soluble U-40 and U-100 insulin after a) subcutaneous injection, b) during continuous subcutaneous insulin infusion (SCII), and c) a supplementary meal bolus.

Comparison of the pharmacokinetics of three concentrations of insulin aspart during continuous subcutaneous insulin infusion (CSII) in a pig model

“…A range of studies have described concentration‐dependent absorption kinetics of subcutaneous bolus injection of human insulin . The different studies concerning human insulin, in different concentrations, showed varying outcomes . Several studies displayed a difference between U40 and U100 human insulin while others failed to do so .…”

“…The different studies concerning human insulin, in different concentrations, showed varying outcomes . Several studies displayed a difference between U40 and U100 human insulin while others failed to do so . One of them showed a small but significant difference after 1.5 h, and another showed an initial difference, whereas two studies showed significance at 30 and 45 min after injection .…”

“…It has been suggested that a low concentration of human insulin will result in a faster absorption for a subcutaneous bolus injection . This is on the account of the fact that human insulin formulations with high insulin concentration contain a larger proportion of insulin in the hexamer form.…”

“…Human studies with human insulin U100 (U100 equals 100 U/mL) and U40 (U40 equals 40 U/mL) have not given uniform conclusions. In some studies a difference in absorption was shown while in others this was not observed . It is important to note that in all referenced studies the human insulin was administered by means of a subcutaneous bolus.…”

Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects

“…between 10 and 5000 IU/ml [5] slower absorption of more concentrated insulin was most clearly demonstrated. Reports concerning differences in pharmacokinetic properties between 40 IU/ml insulin (U40) and 100 IU/ml (U100) have been inconsistent, mainly due to small sample sizes [6][7][8]. The following study assesses the impact of a 2.5-fold increase from U40-to U100-insulin on insulin absorption from the subcutaneous depot, as well as confounding anthropometric variables in a large sample of healthy subjects.…”