Pharmacokinetics and pharmacodynamics of lispro-insulin in hemodialysis patients with diabetes mellitus.
OBJECTIVE
Lispro-insulin, after subcutaneous injection in patients with normal renal function, is absorbed faster and has a faster onset of action when compared to regular insulin. However, the pharmacokinetics and pharmacodynamics of lispro-insulin in renal failure have not yet been investigated.


METHODS
Eight patients with diabetes mellitus on long-term hemodialysis received an individualized dose of regular insulin or lispro-insulin in a crossover design. Blood glucose and insulin concentrations were measured before and after the subcutaneous insulin injections.


RESULTS
Plasma insulin concentrations increased faster (time of maximum concentration tmax 20 vs 40 minutes, p = 0.01) and were higher (standardized maximum concentration Cmax/D 13.6 vs 6.1 microU/ml/U, p = 0.01) after lispro-insulin compared to regular insulin. The area under the curve, clearance and parameters of the hypoglycemic action for the 2 insulin products did not differ significantly, but there was a trend to minimum blood glucose level (time of the blood glucose minimum, Gtmin) to occur earlier with lispro-insulin (120 vs 210 minutes, p > 0.05). Differences in elimination half-life and volume of distribution were explained by flip-flop pharmacokinetics in the case of regular insulin.


CONCLUSIONS
In hemodialysis patients with diabetes mellitus, lispro-insulin is absorbed faster than regular insulin. Differences in the effects of lispro-and regular insulin can be explained by the differences in pharmacokinetics.
Czock
D
D
Nephrology Division, University Hospital, Ulm, Germany.
Aisenpreis
U
U
Rasche
F M
FM
Jehle
P M
PM
D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D061268:Insulin Lispro; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro