Drug Targeting Organ-Specific Strategies

13.2 Pharmacokinetics and Pharmacodynamics, Modelling, Simulation, and Data Analysis 335
fect, and that any therapeutic or toxic effect is due to the released or activated drug.This does
not take into account the possibility of using intrinsically active carriers, which not only deliver
the coupled drug to the appropriate site, but also contribute to the overall therapeutic
effect, an approach known as ‘dual targeting’ [9].
13.1.3 Scope of this Chapter
The aim of this chapter is to provide an overview of the application of PK and PK/PD modelling
and analysis to the field of drug targeting research. For those readers not familiar with
the general principles of pharmacokinetics and pharmacodynamics, modelling, simulation,
and data analysis, these topics are described in some detail in Section 13.2. These methods
can be used for advanced PK and PK/PD modelling and analysis, as well as for conventional
analysis of plasma concentration–time profiles of drugs, drug carriers, and drug–carrier conjugates.
Conventional pharmacokinetic approaches, including descriptive methods for the
evaluation of the concentration or concentration ratio profiles in different tissues, are not
dealt with in this chapter.
The particular models used in drug targeting research are dealt with in Section 13.3, and
quantitative measures of the effectiveness of drug targeting are described in Section 13.4, followed
by a discussion relating to their application in Section 13.5.
Drug targeting by direct regional drug administration, controlled drug release, and pharmacokinetic
modelling and analysis of in vitro experimental data, are outside the scope of
this chapter. For the sake of completeness, some references to relevant papers in these areas
are given in Section 13.6. After a short section (13.7) on software for pharmacokinetic modelling
and data analysis, the perspectives of the application of PK and PK/PD modelling are
discussed (Section 13.8).
13.2 Pharmacokinetics and Pharmacodynamics, Modelling,
Simulation, and Data Analysis
13.2.1 Pharmacokinetics
13.2.1.1 Pharmacokinetic Processes
‘Pharmacokinetics’ (PK) can be defined as the study of the mechanisms and kinetics of drug
disposition in the body (acronym ‘LADME’), and includes the following:
• Liberation of drug from the dosage form. For example, the dissolution of drug from a
tablet;
• Absorption, the transport from the site of administration to the general circulation. For example
the transport of a drug from the gastrointestinal lumen, via the portal vein and the
liver to the central venous blood pool;