Figure 1.
Pharmacokinetic/pharmacodynamic model. PK component: 1-compartment model with first-order absorption and different Ka for U-500R and U-100R, proportional error structure, covariates: dose identified as a significant covariate contributing to interindividual variability of Ka and Clearance; and weight identified as significant for Vd. Sequential model: Pharmacokinetics fixed inputs into pharmacodynamic model. PD component: Effect compartment model with Emax; proportional error structure, covariates: BMI identified as a significant covariate contributing to interindividual variability of Emax. Abbreviations: Ce, concentration in effect compartment; Cs, serum insulin concentration; Ka1, absorption rate constant for U-100R; Ka2, absorption rate constant for U-500R; K20, elimination rate constant from the central (serum) compartment; K23 and K32, distribution rate constants between the serum and effect compartments; SC, subcutaneous.