GENERAL PHARMACOLOGY OF INSULIN LISPRO IN ANIMALS

[Lys(B28),Pro(B29)]-human insulin (insulin lispro, CAS 133107-64-9, LY 275585, Humalog(R)) is a quick acting insulin analog which is currentl y undergoing clinical evaluation for the treatment of diabetes. The po tential secondary pharmacological activity of insulin lispro was profi led in studies for the evaluation of effects on the central and autono mic nervous system, the cardiovascular system, urine and electrolyte e xcretion, and gastrointestinal function. In vivo doses ranged from 0.0 3 to 10 U/kg, administered by the subcutaneous route, while pharmacolo gic activity in vitro was examined in smooth and cardiac muscle at con centrations of 1 x 10(-9) to 1 x 10(-5) mol/l. Insulin lispro exhibite d secondary pharmacological activity in central nervous system tests o nly at higher doses with the most prominent observations being sedatio n and decreased responsiveness. Insulin lispro was essentially inactiv e in tests of autonomic (smooth and cardiac muscle), cardiovascular (m ean arterial pressure, heart rate, systolic pressure, diastolic pressu re, and pulse pressure), renal (urine and electrolyte excretion) and g astrointestinal (motility) function. In summary, insulin lispro had mi nimal effect in these pharmacodynamic studies indicating that insulin lispro has minimal potential to produce adverse pharmacological side e ffects at clinically relevant doses.