After distribution has occurred and the concentration of drug in plasma is in equilibrium with the extravascular compartment, the levels in plasma and tissues fall in parallel as the drug is eliminated from the body.
Drug elimination usually occurs in individual organs, primarily the kidney and the liver. Only drug in the vascular compartment can be cleared during each pass through an organ.
Most drugs are eliminated as a first-order process.
For practical purposes, a first-order elimination process is complete in 4-5 half-lives.
Clearance from the total body (Cl) is the sum of the clearances from all organs of elimination:
Cl =
= (renal clearance) + (hepatic clearance) + (other organ clearances)
The individual organ clearances can be calculated from the extraction ratio for that drug and organ and the total plasma flow to the organ.
It is the best measure of the efficiency of the elimination processes.
For simple 1st-order models:
clearance in L per hour (or mL per minute) =
= ((0.693) * (volume of distribution) / (drug half-life))
