Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmaco-therapeutic group: Drugs used in diabetes, insulins and analogues for injection, intermediate or long acting combined with fast acting. ATC Code: A10A D04.

The primary activity of insulin lispro is the regulation of glucose metabolism.

In addition, insulins have several anabolic and anti-catabolic actions on a variety of different tissues.
Within muscle tissue this includes increasing glycogen, fatty acid, glycerol and protein synthesis and amino acid uptake, while decreasing glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism and amino acid output.

Insulin lispro has a rapid onset of action (approximately 15 minutes), thus allowing it to be given closer to a meal (within zero to 15 minutes of the meal) when compared to soluble insulin (30 to 45 minutes before). The rapid onset and early peak of activity of insulin lispro is observed following the subcutaneous administration of Humalog Mix50. Humalog basal has an activity profile that is very similar to that of a basal insulin (NPH) over a period of approximately 15 hours.


In the figure below the pharmacodynamics of Humalog MIX50 and BASAL are illustrated.




The above representation reflects the relative amount of glucose over time required to maintain the subject's whole blood glucose concentrations near fasting levels and is an indicator of the effect of these insulins on glucose metabolism over time.

The glucodynamic response to insulin lispro is not affected by renal or hepatic function impairment.
Glucodynamic differences between insulin lispro and soluble human insulin, as measured during a glucose clamp procedure, were maintained over a wide range of renal function.

Insulin lispro has been shown to be equipotent to human insulin on a molar basis but its effect is more rapid and of a shorter duration.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
The pharmacokinetics of insulin lispro reflect a compound that is rapidly absorbed, and achieves peak blood levels 30 to 70 minutes following subcutaneous injection. The pharmacokinetics of insulin lispro protamine suspension are consistent with those of an intermediate acting insulin such as NPH. The pharmacokinetics of Humalog Mix50 are representatives of the individual pharmacokinetic properties of the two components. When considering the clinical relevance of these kinetics, it is more appropriate to examine the glucose utilisation curves (as discussed in 5.1).

Insulin lispro maintains more rapid absorption when compared to soluble human insulin in patients with renal impairment. In patients with type 2 diabetes over a wide range of renal function the pharmacokinetic differences between insulin lispro and soluble human insulin were generally maintained and shown to be independent of renal function. Insulin lispro maintains more rapid absorption and elimination when compared to soluble human insulin in patients with hepatic impairment.