Drug Candidates for Effective Targeting

Despite the promising applications of PK and PK/PD modelling in many fields of drug research [3,49] and drug utilization [29], awareness of their limitations is necessary. Among others, the following aspects may interfere with successful PK and PK/PD modelling and analy- 

Inter-individual variability in pharmacokinetics, in particular with respect to clearance [10]. Little is known about the variability of transport to the target site and removal from the target site. Population analysis approaches in PK and PK/PD [50-52] may be helpful in 

Inter-individual variability in pharmacodynamics. Although over the last 30 years it has been the common view that the opposite holds true, Levy demonstrated that PD variability in humans is extensive, reproducible and usually more pronounced than PK variability [53,54]. 

Intra-individual variability, for example due to up- or downregulation of various proteins after multiple dosing, including receptors, carriers and enzymes, resulting in, amongst other effects, the development of tolerance. 

Complexity of the models, making selection of the most appropriate model difficult (Section 13.2.8.6). 

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