Regular human insulin
Human regular insulin was introduced in 1982, as the first product of bio-engineering. Despite the fact that the practical differences between the (then already highly purified) animal insulins and human insulin were limited, it did not take long for the animal insulin preparations to be replaced by their human counterparts. This was partly the result of strong marketing from those who produced the human insulin and partly the result of the intuitive notion that because it was human, it was bound to be better.
Practical use of regular human insulin
Regular human insulin can be injected subcutaneously, intramuscularly, and intravenously. As in physiological situation in the pancreas, in the clinical preparation a little Zinc is present. Insulin has a tendency to self-associate to hexamers (six insulin molecules bound together) around a Zinc atom, which improves water solubility. However, this results in a slight delay in the absorption of regular insulin when injected subcutaneously; it does not materially affect intravenous injection.
Subcutaneous use After s.c. injection insulin levels peak after about 90 minutes and then slowly dissipates in 4 to 6 hours; metabolic action peaks after 2 to 3 hours. Because of this relatively slow onset of action, it is recommended to inject regular insulin 30-45 minutes before the meal to have the insulin peak coincide better with the meal-related rise in glucose. However, the evidence for this recommendation is poor, and for reasons of practicality many patients tend to ignore this advice. When using higher dosages (above approx. 50 IU) the rapidity of action tends to diminish, so it is recommended to split the dose in two separate injections (see also Pharmacokinetics and -dynamics of insulin absorption).
Intravenous use After i.v. injection regular insulin has an immediate peak, with a plasma half-life of about ten minutes. This implies that to maintain steady-state insulinemia a continuous intravenous infusion is necessary. For instance, in the setting of diabetic keto-acidosis, a common approach would be to give a bolus of 0.05-0.1 IU/kg, followed by a continuous infusion of 0.05-0.1 IU/kg/hr.
Intramuscular use Compared to s.c. use, absorption and metabolic action following intramuscular use peaks earlier (after 1-2 hours). However, absorption following intramuscular injection is far more variable (blood flow being dependent on muscle activity), so it is not the preferred mode of administration. It can however be used as an alternative route of administration in those with high glucose or diabetic keto-acidosis when s.c. absorption fails as a result of dehydration.