Modeling of Pharmacokinetic Profiles of Insulin Aspart and Biphasic Insulin Aspart 30/70

Abstract This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins—insulin aspart and biphasic insulin aspart 30/70—to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight‐based dosing and the dose and body‐weight effects on the parameters. The model‐based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1‐compartment model with a combination of zero‐ and first‐order absorptions, with absorption lag for the soluble form of insulin aspart and first‐order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin.