Concept of renal clearance introduced by Thomas Addis and formalized by Donald D. Van Slyke (1928)
Core Principles & Analysis
Originally described for renal function by Thomas Addis and Donald Van Slyke, total systemic clearance (CLtot) is the proportionality factor relating plasma drug concentration (Cp) to the rate of drug elimination (Rate = CL · Cp).
Organ clearance is bounded by organ blood flow (Q) and the intrinsic extraction ratio (E): for high-extraction hepatic drugs (E > 0.7, such as propranolol or lidocaine), clearance is limited by liver blood flow (~90 L/h), whereas for low-extraction drugs (E < 0.3, such as warfarin), clearance depends on unbound fraction (fu) and intrinsic CYP450 enzyme activity (CLint).
Because steady-state average plasma concentration during chronic dosing equals Css,avg = (F · Dose / τ) / CL, clearance is the single pharmacokinetic parameter that determines the maintenance dose rate required to sustain a target plasma exposure.