Evaluation of insulin self-dissolving micropiles by PK/PD analysis

PK/PD analysis was performed after percutaneous administration of insulin self-dissolving micropiles (SDMP) where chondroitin sulfate was used as a base. PK/PD model composed of 1-compartment open model with first-order absorption process and sigmoidal Emax model was used to simulate the time courses of both plasma insulin and glucose levels after percutaneous administration to dogs, 2.0 IU/dog. The Akaike’s information criterion (AIC) were 249.33 ± 13.00, though AIC was 259.55 ± 11.95 for the 2-compartment open model that was directly linked to sigmoidal Emax model. The mean first-order absorption and elimination rate constants of insulin with SDMP were 7.59 ± 3.93 h− 1 (k01) and 1.31 ± 0.66 h− 1 (k10). For subcutaneous (sc) injection of insulin solution, k01 and k10 were 9.72 ± 5.67 h− 1 and 1.60 ± 0.45 h− 1. PD parameter values from insulin SDMP were 148.5 ± 71.9 pg/mL for EC50 and 3.11 ± 1.41 for γ. These results suggested that insulin SDMP has almost the same PK characteristics as sc injection preparation.