Zero order elimination
When therapeutic concentrations of a drug saturate the elimination mechanism(s) primarily responsible for eliminating that drug, then as the drug is eliminated and its concentration falls, the proportion of the eliminating proteins occupied (i.e. b/Bmax) remains at or close to 100%. Therefore, the rate of elimination does not fall. As such, a constant AMOUNT of drug is eliminated in unit time, rather than a constant PROPORTION of drug (as is the case with first order elimination). So a graph of plasma concentration versus time will be a straight line with a negative slope. Only for the last brief period of elimination, when the elimination mechanism is no longer saturated with drug, does elimination occur with first-order (i.e. concentration-dependent) kinetics. An example of zero order elimination is clearance of ethanol.
When low therapeutic concentrations of a drug almost saturate the primary elimination mechanism(s), and a higher therapeutic concentration does saturate the primary elimination mechanism(s), the drug is said to display dose-dependent kinetics. Drugs displaying this behaviour may show a marked increase in elimination half life at higher therapeutic doses compared with lower therapeutic doses.
