Drug Targeting Organ-Specific Strategies

QC
QR
QT
QE
RC
central
compartment
RR
response (target)
compartment
RT
toxicity
compartment
RE
elimination
compartment
CLR
CLT
CLE
13.3 Pharmacokinetic Models for Drug Targeting 355
Figure 13.4. Model of Hunt, adapted from reference [6] (Section 13.3.2). The model describes the fate
of the active drug (D) only. It consists of four compartments: A central compartment (V C) representing
blood and all other tissues not accounted for by the other three compartments, a response (target)
compartment (V R) representing all tissues containing target sites for the desired response, a toxicity
compartment (V T) representing tissues where the cascade of events leading to a toxic response is
initiated, and an elimination compartment (V E) representing the eliminating organs, excluding the
elimination sites in the response and toxicity compartments. Each compartment is characterized by a
volume of distribution V, a blood flow Q (where Q C = Q R +Q T + Q E), and, except for the central
compartment, an elimination clearance CL. Drug delivery is designated by input functions R in the four
compartments. Drug targeting and conventional drug administration are modelled by changing the
relative contributions of R C, R R, R T, and R E. When R C = R T = R E = 0, the drug carrier is an ideal targetspecific
carrier.
drug effect after the conclusion of drug administration.To evaluate the time course of action,
a full model, including the pharmacokinetic behaviour of the drug–carrier conjugate, should
be used, for example the model of Stella and Himmelstein (Section 13.3.1) or the model of
Boddy et al. (Section 13.3.3).