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

Insulin lispro is a monomeric analogue of human insulin, produced by genetic engineering, and has been reported to have a more rapid absorption following 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 was designed originally for insulin, to measure insulin lispro potency was evaluated in this investigation. A random-dose bioassay protocol, in which insulin lispro and two insulin standards were administered intravenously in a random sequence, was used and validated in nine conscious healthy rabbits. The decline in blood-glucose levels, following the intravenous injection of a dose of insulin or its lispro analogue, was monitored by a continuous glucose monitoring system. A glucose response curve was generated, from which various pharmacodynamic parameters were determined. Compared with the insulin standards, the potencies of insulin lispro determined from nadir, basal glucose normalized nadir, glycaemic reduction and ABGC (area of the blood-glucose response curve under baseline) were observed to have mean (95% confidence limits) values of 97.0 (69.5-124.6)%, 106.3 (72.4-140.2)%, 949 (51.8-138.0)% and 102.4 (76.3-128.5)%, respectively. In addition, the coefficients of variation for correspondent parameters were 36.9, 41.5, 59.1 and 33.2%, respectively. The results indicated that the hypoglycaemic potency calculated from the ABGC values was the most accurate (102.4%) with the least coefficient of variation (33.2%). In conclusion, the potency of insulin lispro can be determined accurately from the ABGC values measured by the random-dose bioassay used.