Effects of change in elimination on various parameters of the two‐compartment open model

The various parameters of the two‐compartment open model which are employed commonly in pharmacokinetics can be classified into three groups, based on their mathematical behavior, when a change in the elimination constant (K_el) is induced but the distribution constants (k₁₂, k₂₁, and V_c) of the drug are maintained unchanged. At a given dose of drug, certain parameters (V_Dss and C_p°) remain constant because they are independent of k_el. Other parameters (Area, Cl_B, D₁, D₂, and D_T) change exactly in proportion of k_el because these values are a direct linear function of k_el. A third group (α, β, A, B, V_Dβ, V_Darea, V_B, f_c, and t_1/2β) are nonlinear or hybrid parameters; they change in value disproportionately with k_el. Absolute changes in distribution space or elimination constants at a given dose level cannot be quantitated with these hybrid terms individually. They reflect the degree of equilibration of a drug between compartments and should be restricted to use as proportionality terms for relating the time course of plasma and body levels of drug.