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The kinetics of insulin administration by insulin pens.

Insulin pens deliver insulin more slowly than syringes because of compressible elements of the insulin cartridges, especially air bubbles. The time required for a pen to deliver 20 Units of insulin increased with increasing air in the cartridge as determined by two independent techniques. The first technique involved no back pressure and was done by injection of [125I]-iodoinsulin onto absorbent paper on a constant angular velocity turntable. The second technique involved the normal back pressure of subcutaneous tissue and was done by robotic, timed injections of [125I]-iodoinsulin into full thickness pigskin. Air dramatically reduced the delivery of insulin in the five seconds that patients normally wait for injection by an insulin pen. Accumulation of more than 50 microliters of air results in a delivery of an unacceptably low percentage of insulin: with 200 microliters of air, a patient would get only 37% of the expected dose. Thus, a patient who injects 20 Units of insulin and withdraws the needle after the recommended 5 seconds would receive only 7.4 Units if there were 200 microliters of air in the cartridge. Since we found that 42 of 50 commercially available insulin cartridges contained air bubbles at purchase (average estimated to be 50 microliters), additional air entering the cartridge could lead to serious underdosing. Previous studies have demonstrated that air accumulates in insulin cartridges when the needle is left on the pen between injections. Therefore, for safety reasons, patients should be strongly advised to remove the needle immediately after each injection as recommended by the manufacturer.