Figure 2.

Structural model consisting of two-compartment models for both riociguat and M1. The clearance of both riociguat and M1 is split into a renal component (filtration and excretion) and a nonrenal component, which for riociguat is further divided into conversion to M1 and a remaining nonrenal component. The oral dose enters the central compartment with first-order kinetics with a rate constant KA. A small fraction of the dose is metabolized presystemically, as described by the additional rate constant K13. Both absorption processes start after a common lag time. KA: absorption rate constant; K13: kinetic constant for the presystemic metabolism (<1%); M1: main metabolite of riociguat; V_D: volume of distribution. *Other than conversion to M1; ^†filtration and secretion.