2019 PharmSci 360
For a half-century clearance concepts have been utilized in pharmacokinetics to understand the relationship between dose administered and time-course of systemic concentrations. Here we counter the hypothesis that organ clearance determined as hepatic blood flow multiplied by extraction ratio is model independent. This hypothesis ignores the fact that for the same entering and exiting concentrations, exposure within the liver is not the same for the different models of hepatic elimination, and in pharmacokinetics clearance has always been determined as the amount of drug eliminated divided by the exposure (integrated concentrations) driving that elimination. Clearance is always model dependent.