FIG. 3

Effect of a change in clearance on the extent of drug accumulation during chronic dosage, and on the rate of attainment of steady state. In the control condition, clearance = CL0, and elimination half-life = 1.0 days. After initiation of a constant dosage regimen at time = 0 (solid line), the steady-state plasma concentration is 1.0 units, and approximately 4 days (4 {ewc MVIMG, MVIMAGE,!times.bmp} t1/2) are required for steady state to be more than 90% attained. Assuming the same volume of distribution and dosing rate, reduction of clearance relative to the control value (dashed lines) increases the steady-state plasma concentration and prolongs the time necessary to attain steady state. When CL = 0.5 {ewc MVIMG, MVIMAGE,!times.bmp} CL0, the steady-state plasma concentration is 2.0 units, half-life is 2.0 days, and 8 days (4 {ewc MVIMG, MVIMAGE,!times.bmp} t1/2) are necessary for 90% attainment of steady state.

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published 2000