[Untitled]

Basic indirect pharmacodynamic models for agents which alter the generation of natural cells based on a life-span concept are introduced. It is assumed that cells (R) are produced at a constant rate (kin), survive for a specific duration TR, and then are lost. The rate of cell loss must equal the production rate but is delayed by TR, A therapeutic agent can stimulate or inhibit the production rate according to the Hill function: 1 ±H(C(t) ) where H(C(t)) contains capacity (Smax) and sensitivity (SC50) constants and C(t) is a pharmacokinetic function. Thus an operative model is dR/dt = kin • [1 ± H(C (t))J-ktn • [1 ± H(C(t-T R))]