Criticism of pharmacokinetic clearance concepts

The value of pharmacokinetic parameters is confirmed by clinical impacts. Drug dosage recommendations are usually derived from the one-compartment model and linear first-order kinetics. These are described by the parameters bioavailability, volume of distribution, and elimination half-life. Thus, elimination half-life and volume of distribution are the most important clinical pharmacokinetic parameters and the one-compartment model is the most universal pharmacokinetic concept. Drug clearance provides no further information. To evaluate drug clearance, the AUC must be extrapolated. This requires the assumption of a compartment model. The intrinsic hepatic clearance cannot be equated with hepatic metabolism capacity. Therefore, drug clearance does not appear to be a superior pharmacokinetic parameter.