Pharmacokinetic and pharmacodynamic assessment of novel and biosimilar insulins

Abstract

Background Advances in insulin therapy have resulted in a wide and ever-expanding range of rapid-acting and long-duration insulins. Development of novel insulins e.g. through application of recombinant DNA technology or based on advanced insulin formulation platforms aim to improve insulin pharmacokinetics and pharmacodynamics. Demonstration of clinical safety and efficacy is required as a novel insulin progresses from preclinical to clinical development. The euglycemic clamp technique is the method of choice for determining time-action profiles of new insulins and has a central role in the pharmacodynamic evaluation of biosimilar-also known as follow-on-insulins. Key Methods Available methods may be usefully considered as (a) indirect and (b) direct assessments of insulin pharmacokinetics and pharmacodynamics. The advent of novel insulins and insulin delivery systems, e.g. inhaled insulin, adjunctive measures to alter insulin pharmacokinetics, and the development of biosimilar insulins, necessitate careful quantification. The euglycemic clamp is unrivalled in providing combined pharmacokinetic and pharmacodynamic information that informs the development of new insulins and optimization of insulin therapy. The euglycemic clamp technique is also crucial for the pharmacodynamic evaluation of biosimilar insulins.