The larger the clearance, the higher the rate of elimination possible at any given concentration (see Fig. 23a) and therefore the lower the concentration needed to achieve an elimination rate equal to a particular rate of input, Rin, (see Fig. 23b), i.e.13 c=Rin/CL.
Fig. 23 The relationship between the rates of input and elimination, substrate concentration in ISF and clearance. At steady-state the rate of elimination must equal the rate of input. The horizontal dashed lines show rates of input (R1, R2, R3 and Rin). The clearance, CL, is the slope of the line for the plot of rate of elimination versus concentration. Lines for three values of clearance (CL1, CL2 and CL3) are shown. a To achieve the steady-state concentration, cisf, clearance must be higher to balance the higher rate of input i.e. the rate of input required is proportional to clearance. b For a given rate of input, the steady-state concentration is inversely proportional to CL (compare the three steady state concentrations c1 c2 and c3 achievable for the three clearance values CL1, CL2 and CL3). c For a given clearance the steady-state concentration is proportional to the rate of input. Changes in input need not produce changes in concentration if the clearance can be changed, e.g. for the increase from R1 to R3 shown in a the concentration would be constant if the clearance could be increased from CL1 to CL3