Pharmacokinetics of capacity-limited systems.

Nonlinearities are commonplace in pharmacokinetics and most frequently occur because of a limited concentration of biological material available for interaction with relatively high concentrations of drugs. The Michaelis-Menten-type function can be applied to metabolism, transport, and binding phenomena that display capacity-limitation. Nonlinear systems can be handled with differential equations (directly or converted to linear form), integrated equations (in non-closed form) or with relatively new area/moment or MRT relationships. Drug disposition studies should include several dose levels and recommendations are provided for detecting the presence of one or more nonlinear absorption or disposition processes in typical experimental data.