Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification

作者：Peletier Lambertus A^*; Gabrielsson Johan

来源：Journal of Pharmacokinetics and Pharmacodynamics, 2012, 39(5): 429-451.

DOI：10.1007/s10928-012-9260-6

• Target
• Receptor
• Antibodies
• Drug-disposition
• Michaelis-Menten
• Quasi-steady-state
• Quasi-equilibrium
• Singular perturbation

In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of different phases in the temporal behaviour of the system. These approximations are used to estimate model parameters, give analytical approximations of such quantities as area under the ligand curve and clearance. We formulate conditions under which a suitably chosen Michaelis-Menten model provides a good approximation of the full TMDD-model over a specified time interval.

• 出版日期2012-10