Case Study
Saccadic Eye Movements and Pupillometry Help Characterize Pharmacodynamic Drug Effects
Download Full Case Study:
•Case Study: Saccadic Eye Movements And Pupillometry Help Characterize Pharmacodynamic Drug Effects
Over the last 20 years there ha s be en a significant change in the approach that is taken to the early stages of clinical development. The initial studies of a molecule in man are no longer focused purely on safety, tolerability, and PK but are layering in techniques to better understand and characterize a molecule in terms of putative efficacy, wanted and undesired side effects, time course of pharmacodynamic effects, and competitive performance to existing therapies.
The drive for the change has come from the industry itself which has been faced with rising R&D expenditures and a high fail rate of molecules in expensive patient trials. The pressure has grown to reduce development time lines, decrease overall development costs and make go/no-go decisions on compounds at an earlier stage.
At the forefront of this change has been the inclusion of often simple physiological measures into the first in man trials that can be used to provide some of this pivotal information. To illustrate the use of these techniques this article will explore how two simple techniques involving measurements from the eyes, saccadic eye movements, and pupillometry, are being applied to investigate the side-effect profile of compounds, better understand the mechanisms involved in the pathophysiology of CNS disease states and demonstrate target engagement of drugs.
Technique one: saccadic eye movements
A saccadic eye movement, or saccade, occurs when a human changes their direction of gaze from one point to another. The decision to initiate a saccade is under voluntary control, however, once the saccade is initiated the speed that the
eye moves is completely involuntary with no central
CNS influence.
Saccadic velocity has been shown to be adversely effected by compounds that cause sedation. A number of studies have reported that ethanol will induce a decrease in saccadic velocity at very low doses where the subjects are unable to qualitatively self-report feelings of sedation. 1 Decreases have similarly been shown when subjects have received compounds that induce symptoms of sedation such as benzodiazepines and opiates.
Technique two: pupillometry
Measurement of pupil diameter has been shown to be a
sensitive and objective marker of autonomic activation4 and
a validated marker of drug activity on the autonomic nervous
system.
In this test, subjects sit in front of an infrared camera under standard low-light conditions. The camera is focussed on the pupil. Measurement of initial pupil diameter is recorded directly and the pupillary constriction response (latency, amplitude, and duration) to a flash of light is also measured.,/p>
Download Full Case Study:•Case Study: Saccadic Eye Movements And Pupillometry Help Characterize Pharmacodynamic Drug Effects
