Computational simulations of local vascular heparin deposition and
distribution.
Lovich, Mark A.
Harvard University-Massachusetts Institute of Technology, Division
of Health Sciences and Technology, Cambridge, MA
APStracts 3:0152H, 1996.
Local vascular drug delivery systems provide elevated concentrations
in target arterial tissues, while minimizing systemic side effects,
however, definition of their precise pharmacokinetics remains
elusive. The standard labeled tracer assays used in experimental
vascular pharmacokinetic studies of these systems are limited because
they quantify the arterial average drug concentration as opposed to
transmural concentration profiles, require many animal experiments to
elucidate the time varying deposition, and track label rather than
intact biologically active drug. In this study, computational
simulations of drug deposition and distribution in vascular tissues
following release from these systems have provided two important
insights. First, simulations of drug transport and deposition within
arteries that were uniformly loaded with heparin predicted that most
of the drug is cleared in less than 1 hour, illustrating the need for
sustained modes of delivery. Second, some of the limitations of
labeled tracers can be over come by combining experimental data with
simulations which provided high spatial resolution. This enabled us
to describe the kinetics of the deposited drug, and distinguish
soluble from reversibly bound, and internalized drug within cells.
The latter can help differentiate biologically viable drug from its
committed inactive form or metabolites. These points have been
illustrated through simulations of a novel endovascular hydrogel
heparin delivery system that has been applied to the porcine coronary
artery (27). The basic models used in these simulations are
generalized, and with the appropriate boundary conditions, binding,
and distribution constants can be used to study the physical
interactions between any compound and tissue.
Received 6 February 1996; accepted in final form 5 April 1996.
APS Manuscript Number H112-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96