Clearance (CL)
Clearance is the volume of plasma from which a drug is completely removed per unit time. It sets the average concentration for a given dose rate and is the parameter most tied to exposure.
Definition
Clearance (CL) is the volume of plasma that is completely cleared of drug per unit time, in units such as L/h or L/day. It is the proportionality between elimination rate and concentration.
What it determines
For linear PK, AUC after an intravenous dose is the dose divided by CL, and at steady state the average concentration is the dose rate divided by CL. Anything that raises CL, such as a higher body weight, lowers exposure for a fixed dose.
Antibodies
Monoclonal antibodies are eliminated mainly by catabolism, and clearance can also include target-mediated elimination (see target-mediated drug disposition). Some antibodies show a clearance that falls over time on treatment.
On this site
The reimplemented pembrolizumab model has a typical clearance of 0.22 L/day with a body-weight exponent of 0.595, and the nivolumab model a clearance that decreases over time by up to about 26%; see the anti-PD-1 analysis. The mosunetuzumab reimplementation uses a time-varying clearance as an empirical description. See also body weight as a covariate.
Frequently asked questions
What are the units of clearance?
Volume per time, for example L/h or L/day.
Why can the clearance of an antibody change over time?
In the models used here the decrease is an empirical description that reproduces the observed time course; it is not a mechanistic model of disease or treatment response.