Insulin lispro: In-vivo potency determination by intravenous administration in conscious rabbits

Insulin lispro is a monomeric analogue of human insulin, produced by geneti c engineering, and has been reported to have a more rapid absorption follow ing subcutaneous injection than insulin. Since it has been shown to have a similar hypoglycaemic action to insulin in clinical studies and comparable properties in radioimmunoassay, the feasibility of using a bioassay which w as designed originally for insulin, to measure insulin lispro potency was e valuated in this investigation. A random-dose bioassay protocol, in which insulin lispro and two insulin st andards were administered intravenously in a random sequence, was used and validated in nine conscious healthy rabbits. The decline in blood-glucose l evels, following the intravenous injection of a dose of insulin or its lisp ro analogue, was monitored by a continuous glucose monitoring system. A glu cose response curve was generated, from which various pharmacodynamic param eters were determined. Compared with the insulin standards, the potencies o f insulin lispro determined from nadir, basal glucose normalized nadir, gly caemic reduction and ABGC (area of the blood-glucose response curve under b aseline) were observed to have mean (95% confidence limits) values of 97.0 (69.5-124.6)%, 106.3 (72.4-140.2)%, 94.9 (51.8-138.0)% and 102.4 (76.3-128. 5)%, respectively. In addition, the coefficients of variation for correspon dent parameters were 36.9, 41.5, 59.1 and 33.2%, respectively. The results indicated that the hypoglycaemic potency calculated from the AB GC values was the most accurate (102.4%) with the least coefficient of vari ation (33.2%). In conclusion, the potency of insulin lispro can be determin ed accurately from the ABGC values measured by the random-dose bioassay use d.