ABSTRACT
As early as in the eighteenth century, it was mentioned that drug response (the
duration of mydriasis observed following belladonna administration) depended
on dose size (1), cited after Abdel-Rahman (2). Subsequent pharmacologic
investigations have confirmed the presence of the dose-response relationship
for the majority of drugs. However, drug response is subject to substantial inter-
individual variability. Individuals receiving the same dose or dosage regimen
may demonstrate responses that vary widely in onset, magnitude, and duration.
Dose individualization is, therefore, the ultimate goal for those involved in
drug development and evaluation: pharmaceutical industry, academia, and regu-
latory agencies. However, this does not seem to be an easy task, due to high
between-individual variability (BIV) in pharmacokinetic (PK), pharmacody-
namic (PD), physiological, and pathophysiological processes involved in clinical
manifestation of drug effects. The goal of the late stage of drug development is
thus the selection of a dose or doses to be recommended for therapeutic use,
and the intention is to optimize the dosage and reduce the risk of under-or
overdosing as much as possible.
