Fig. 1.

Schematic representation of the selected pharmacokinetic/pharmacodynamic model. Pharmacokinetics: k_a, first order rate constant of absorption; V_C/F, and V_P/F, apparent volumes of distribution of the central and the peripheral compartments, respectively; CL/F apparent plasma clearance (oral); Q/F, inter-compartmental distribution clearance. pharmacodynamics: DPP4 activity (free receptor) can be synthesized at a zero-order rate (k_syn) and degraded at a first-order (k_deg). E_drug induces activity loss by the receptor binding. C_P, predicted sitagliptin plasma concentration; E_max is the maximum effect; EC₅₀ is the drug concentration need to achieve the 50% of the E_max; h is the hill exponent. 1/k_f represents the expected time delay for the feedback.