Biomedical Engineering Reference
In-Depth Information
Challenges in Ocular Pharmacokinetics,
Pharmacodynamics, and Toxicology
Brian C. Gilger
Abstract
Study of ocular pharmacology, pharmacodynamics, and toxicology is challenging due to the inherent ocular
barriers to drug penetration, small ocular tissue sizes and volumes, and sensitive ocular structures.
Additionally, wide variation of ocular sizes and physiology among animal models complicates simple
translation of results from one species of animal to another. This chapter, and those to follow, will describe
the challenges researchers face regarding ocular pharmacology and toxicology as well as providing them
with practical methodologies for conducting studies, including study design and specialized methodology,
to overcome these challenges and thus improve treatment of ocular disease.
Key words
Ocular pharmacokinetics, Pharmacodynamics, Toxicology, Challenges
1
Introduction
This topic's subject is ocular pharmacokinetics, pharmacodynamics,
and toxicology. There are detailed chapters on study design, analy-
sis, and routes to regulatory approval for various types and routes of
ophthalmic drugs, implants, and devices. The practice of ophthal-
mology can be reduced to the simple goal of getting the right drug
at the appropriate therapeutic dose to the target ocular tissue by a
method that does not damage healthy tissue [
1
]. In treatment of
ocular disease, however, this simple goal becomes more challenging
because of the highly sensitive ocular tissues (e.g., the lens, uveal
tract, and retina) and the presence of tissue barriers to drug penetra-
tion, namely the lipophilic corneal epithelium, the hydrophilic cor-
neal and scleral stroma, the conjunctival lymphatics, choroidal
vasculature, and the blood-ocular barriers [
2
-
8
]. Clearly, pharma-
cokinetics, pharmacodynamics, and toxicology are closely interre-
lated for all organ systems and drugs, but for the reasons discussed
above, the eye poses significantly more challenges than most other
tissues.
By definition,
ocular pharmacokinetics
is the study of the
mechanisms of drug absorption, distribution, metabolism, and
excretion; onset of action; duration of effect; biotransformation;
1
