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. PATIENTS AND 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.

[Advantages of insulin Lispro (short-acting) in terminal kidney failure]. / Vorteile von Insulin Lispro bei terminaler Niereninsuffizienz.

Diabetic management of dialysis patients with end-stage renal failure is often problematic. Renal failure interferes with the metabolism of glucose and insulin. Many of these diabetics have wide fluctuations in their daily blood glucose profile. The kinetics of regular insulin may be appreciably prolonged in consequence of the failure of renal insulin degradation, making the dose-effect profile of the insulin difficult to control, and hypoglycemia more likely. Intensified conventional insulin treatment (ICT) using the short-acting insulin, Lispro, facilitates the calculation of insulin requirements and helps to avoid large fluctuations in blood glucose levels. The present case report illustrates these difficulties in a patient on dialysis, and shows how ICT with Lispro can improve the quality of life of diabetics with renal failure.