Target-Mediated Drug Disposition Revisited: Michaelis-Menten Approximations for Bivalent Drug Molecules.

Abstract

The Michaelis-Menten (MM) approximation of the target-mediated drug disposition (TMDD) model is often used to describe nonlinear pharmacokinetics of monoclonal antibodies, which are, however, bivalent molecules. We analyze a TMDD model for bivalent drugs by means of quasi-steady state approximations, which yield MM approximations in the limit of weak avidity (soluble targets) and strong avidity (cell surface targets), thereby providing a justification for the use of MM approximations for bivalent drugs with slow systemic clearance.