Pharmacokinetic/Pharmacodynamic Modelling in Drug Targeting
Johannes H. Proost · Methods and principles in medicinal chemistry · 2001
Introduction Drug targeting and effectiveness: the role of pharmacokinetics Pro-drugs and drug–carrier conjugates Scope of this chapter Pharmacokinetics and pharmacodynamics, modelling, simulation, and data analysis Pharmacokinetics Pharmacokinetic processes Transport mechanisms Perfusion and permeability Plasma protein binding and tissue binding Pharmacodynamics Model and modelling Pharmacokinetic models Compartmental models Physiologically-based pharmacokinetic (PB-PK) models Compartmental models versus physiologically-based models Principles of modelling Pharmacodynamic models Sigmoid Emax model Growth/kill models Empirical PK/PD relationships Pharmacokinetic/pharmacodynamic (PK/PD) models Simulations Data analysis by modelling Model building Defining the objective function Searching the best-fitting set of parameters Identification of model parameters Goodness-of-fit Model selection Pharmacokinetic models for drug targeting Model of Stella and Himmelstein Disposition of DC Delivery of the DC to the target site Release or activation of D at the target site Removal of D from the target site Release of D at non-target sites Disposition of D Model of Hunt Model of Boddy Model of Rowland and McLachlan Measures of effectiveness of drug targeting Therapeutic availability (TA) Drug Targeting Index (DTI) Targeting Index (TI) Evaluation of effectiveness of drug targeting using PK and PK/PD modelling Effectiveness of an ideal carrier Implications of the DTI concept Drug candidates for effective targeting Limitations of PK and PK/PD modelling Examples of PK modelling in drug targeting In vivo studies In vitro studies Regional drug administration Controlled drug delivery Pharmacokinetic properties of macromolecular carrier systems Software for PK and PK/PD modelling Perspectives and conclusions