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Target-Mediated Drug Disposition

By Fulden Buyukozturk on 10 Oct 2018 (Edited)
Latest activity Edited by Hollis Potter on 7 Nov 2018

This project presents a SimBiology implementation of Mager and Jusko’s generic Target-Mediated Drug Disposition model (TMDD) as described in "General pharmacokinetic model for drugs exhibiting target-mediated drug disposition". Target-mediated drug disposition is a common source of nonlinearity in PK profiles for biotherapeutics. Nonlinearities are introduced because drug-target bindings saturate at therapeutic dosing levels.

Drug in the Plasma reversibly binds with the unbound Target to form drug-target Complex. kon and koff are the association and dissociation rate constants, and clearance of free Drug and Complex from the Plasma is described by first-order processes with rate constants, kel and km, respectively. Free target turnover is described by a zero-order synthesis rate, ksyn, and a first order elimination (rate constant, kdeg). The model also includes an optional Tissue compartment to account for non-specific tissue binding or distribution.

References [1] Mager DE and Jusko WJ (2001) General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J Pharmacokinetics and Pharmacodynamics 28: 507–532.

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