Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with Type 1 (insulin-dependent) diabetes mellitus


These studies were undertaken to assess the influence of storage temperature of insulin vials on pharmacokinetics and pharmacodynamics of a mixture of lente insulin (Monotard HM) and regular insulin (Actrapid HM) injected subcutaneously. Seven subjects with Type 1 (insulin-dependent) diabetes mellitus were studied twice after overnight normalization of plasma glucose. A mixture of lente insulin (0.22 U/kg) and regular insulin (0.11 U/kg) was prepared from insulin vials kept either refrigerated (∼4 °C) or at room temperature (∼18 °C) and injected subcutaneoulsy (abdomen). Euglycaemia was maintained for the following 16 h by glucose infusion at variable rate. With refrigerated insulin, the plasma free insulin peak was greater (53±5 versus 45±6 mU/l) and occurred earlier (2.5±0.2 versus 6±0.3 h), and the glucose infusion rate showed a greater (16.5±1.2 versus 14.5±0.9 μmol·kg−1·min−1) and earlier peak (3.2±0.2 versus 6±0.4 h) as compared to that occurring with the non-refrigerated insulin (p<0.05). However, 6 h after insulin injection, both plasma free insulin and glucose infusion rate were 30% lower with the mixture of refrigerated as compared to that of non-refrigerated insulin (p<0.05). In contrast, when NPH-insulin (Protaphane HM) was mixed with regular insulin and injected in 4 out of the 7 diabetic patients, the storage temperature of insulin vials had no effect on the pharmacokinetics and pharmacodynamics of the mixture. Thus, the storage temperature of insulin vials profoundly influences the effects of the mixture lente/regular insulin, but does not affect the pharmacokinetics and pharmacodynamics of the mixture NPH/regular insulin.


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Perriello, G., Torlone, E., Di Santo, S. et al. Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 31, 811–815 (1988). https://doi.org/10.1007/BF00277482

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Key words

  • Insulin pharmacokinetics
  • insulin pharmacodynamics
  • insulin mixtures
  • glucose clamp
  • insulin absorption
  • regular insulin
  • lente insulin
  • NPH insulin