Effect of saturable binding on the pharmacokinetics of drugs: a simulation

The time-courses of both total and unbound drug concentrations with time were simulated under conditions of saturable binding to either plasma proteins or tissues, or both, following a single intravenous dose. The curves were either linear, convex, or concave, depending upon the extent of distribution and the intrinsic ability of an eliminating organ to remove drug from the body. Saturable binding should therefore be considered whenever data showing nonlinear semilogarithmic decline are to be interpreted.