Fig. 1.

Characteristic ligand versus time graph in target-mediated drug disposition. The concentration of the ligand is measured on a logarithmic scale. In the first phase (A) drug and target rapidly equilibrate, in the second phase (B) the target is saturated and drug is mainly eliminated directly by a first order process, in the third phase (C) the target is no longer saturated and drug is eliminated directly, as well as in the form of a drug–target complex, and in the final, fourth phase (D) the drug concentration is so low that elimination is a linear first order process with direct as well as indirect elimination (as a drug–target complex)