General pharmacology of insulin lispro in animals.
[Lys(B28),Pro(B29)]-human insulin (insulin lispro, CAS 133107-64-9, LY275585, Humalog) is a quick acting insulin analog which is currently undergoing clinical evaluation for the treatment of diabetes. The potential secondary pharmacological activity of insulin lispro was profiled in studies for the evaluation of effects on the central and autonomic nervous system, the cardiovascular system, urine and electrolyte excretion, and gastrointestinal function. In vivo doses ranged from 0.03 to 10 U/kg, administered by the subcutaneous route, while pharmacologic activity in vitro was examined in smooth and cardiac muscle at concentrations of 1 x 10(-9) to 1 x 10(-5) mol/l. Insulin lispro exhibited secondary pharmacological activity in central nervous system tests only at higher doses with the most prominent observations being sedation and decreased responsiveness. Insulin lispro was essentially inactive in tests of autonomic (smooth and cardiac muscle), cardiovascular (mean arterial pressure, heart rate, systolic pressure, diastolic pressure, and pulse pressure), renal (urine and electrolyte excretion) and gastrointestinal (motility) function. In summary, insulin lispro had minimal effect in these pharmacodynamic studies indicating that insulin lispro has minimal potential to produce adverse pharmacological side effects at clinically relevant doses.
Helton
D R
DR
Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana, USA.
Zimmermann
J L
JL
Heim
A
A
Jones
T W
TW
Turk
J A
JA
Kallman
M J
MJ
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000652:urine; D061268:Insulin Lispro; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014882:Water-Electrolyte Balance / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro