Figure 1. Combined PK/VK model used to describe viral kinetics during danoprevir monotherapy.

(A) Schematic of the two-compartment PK model following zero-order absorption of danoprevir. Danoprevir is absorbed, after a lag time T_lag into the central compartment/blood plasma (Q₁) following a zero order absorption law with rate constant Tk₀. Danoprevir is eliminated from the central compartment via a first order elimination process with rate constant k_e, and moves in to and out of the second compartment (Q₂) with forward and backward rate constant k₁₂ and k₂₁, respectively. (B) Schematic representation of the VK model. Danoprevir inside infected cells, I, is considered to partially block viral RNA production with a time varying effectiveness, ε(t), which depends on the danoprevir concentration. Target cells, T, are infected by virus, V, with rate constant β to produce infected cells, I. Infected cells, I, are lost with rate constant δ and virus, V, is cleared from the circulation with rate constant c. In the absence of drug infected cells produce virus with rate p per infected cell.