Pharmacokinetics of insulin administered subcutaneously. Application to treatment by portable pump (1)

Continuous subcutaneous insulin infusion is characterized by a basal insulin delivery rate to which insulin boluses are added. The basal delivery rate maintains a small insulin reserve in the local subcutaneous depot. This reserve averages 2 to 5 times the hourly basal rate at the steady-state which is reached after about 7 hours but depends on numerous factors: subcutaneous blood flow, skinfold thickness, insulin concentration, etc. It explains the pharmacokinetics time-lag of the system, more particularly the similar effects of a basal rate delivered in either a pulsatile/intermittent or a continuous manner, the lack of deleterious effect of a 1-h pump arrest, the 2-h delay before significant metabolic deterioration during a more prolonged interruption of the infusion, the delayed plasma insulin changes when the basal insulin delivery rate is doubled or reduced by half, etc. Insulin boluses pharmacokinetics is not fundamentally different from that of soluble insulin injection in conventional therapy. As an example, insulin boluses should ideally be given 30 min before the meals in order to better prevent post-prandial hyperglycaemia. However, the absence of intermediate zinc-insulin in the system may result in an earlier increase of plasma free insulin levels, which for instance allows a rapid correction of the metabolic alterations induced by a prolonged interruption of the basal infusion rate. This kinetics does not seem to be significantly altered by insulin concentration nor by the profile of the bolus but is affected by the insulin content of the subcutaneous depot at the time the bolus is delivered.(ABSTRACT TRUNCATED AT 250 WORDS