The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection

Abstract

To compare the pharmacokinetics of two different concentrations, containing either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate-acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single-blind, crossover trials were performed using the euglycemic clamp technique. Eighteen healthy volunteers received insulin of either formulation subcutaneously in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood glucose levels were maintained constant by glucose infusions. In the trial using Velasulin, the two different insulin concentrations were equivalent regarding the total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123 +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The glucose requirement was not equivalent in each of the three series.(ABSTRACT TRUNCATED AT 250 WORDS)

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 .…”

“…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.…”

Comparative Pharmacokinetics and Glucodynamics of Two Human Insulin Mixtures 70/30 and 50/50 insulin mixtures

“…Differences between NPH and Regular insulin pharmacokinetics and pharmacodynamics are well-known (14,(16)(17)(18). Mixtures of these two insulins have also been studied, but such studies have generally been limited to 70/30 or mixtures with greater percentages of NPH insulin (18,19). Distinct differences in the serum concentration versus time curves were found between the two mixtures (Fig.…”