![]() ![]() Moreover, the system is written in total variables, i.e. Structurally, a TMDD approximating system is a collection of ordinary differential equations (ODE) and so-called algebraic equations arising from the QE or QSS assumption. The single drug TMDD model with and without approximation was investigated in several manuscripts. Typically, two approaches are applied, the quasi-equilibrium (QE) or the quasi-steady state (QSS) approximation to describe the rapid binding assumption. Since binding of drug to receptor usually occurs rapidly, steady state assumptions can be made to reduce the number of parameters. In general a TMDD system is over-parameterized for parameter estimation. Also minimal physiologically based PK models were extended with TMDD mechanisms. TMDD behavior is used in several scenarios, such as binding of one drug to two targets, for antibody-drug conjugates, or receptor mediated endocytosis, just to name a few. The TMDD approach for a single drug finds broad application in PK modeling, see for a list of compounds. Target-mediated drug disposition (TMDD) describes the phenomenon where the pharmacokinetics (PK) of a drug is significantly affected by the high affinity binding properties of that drug to its target (such as a receptor, enzyme or transporter). ![]()
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