Head of Cardiovascular Pharmacology Aptuit R&D Medicine Research Centre
"One of the major hurdles in the development of novel drug candidates is the potential for central nervous system (CNS) and cardiovascular side effects.
The conventional approach in the Pharmaceutical Industry is to investigate potential for such adverse effects in separate studies; rodents (mainly rats) are the first choice of species to detect behavioral and neurological effects (using for example the so called Irwin test), whilst non rodents predominate for the assessment of cardiovascular effects.
The most commonly used non-rodent species in safety assessment studies is the dog. Specifically, the beagle is the standard breed employed, and the development of telemetric techniques to monitor physiological parameters in conscious unrestrained animals is now well established. This technique has major advantages for eliminating the deleterious influences of anesthetic and restraint-induced stress associated with the use of other models available.
Our collaboration with NOTOCORD started in 2001 in both cardiovascular and respiratory areas, and in 2006 we established a new model using dogs which allows the integration of both neurobehavioral and cardiovascular assessments within one study.
This was possible using the NOTOCORD-hem Evolution® 4.2 that allows the simultaneous recording of video as well as cardiovascular parameters using telemetry (Figure 2). A direct neurological examination was also implemented to allow a complete evaluation of neurobehavioral function.
There are two main advantages adopting this innovative methodology. Firstly, there is a remarkable reduction of animal use when compared to the number required using separate studies since the new method allows the reuse of animals after an appropriate washout period.
Secondly, this refined methodology allows the evaluations to be integrated into the same species, recognized to reliably predict adverse effects in humans.
Obtaining responses in the same animal (with each dog acting as its own control, when using Latin cross-over design in particular) achieves a very high statistical power even with a relatively small group size.
Finally, the use of NOTOCORD-hem Evolution® provides a powerful method to facilitate data interpretation by enabling simultaneous review of cardiovascular telemetry data and video images."
Nicola Fasdelli has a Degree in Chemistry and Pharmaceutical technologies. His background is in the cardiovascular area, holding positions within GlaxoSmithKline for 12 years before joining Aptuit.
Aptuit is a global provider dedicated to science, committed to quality as a drug development partner for the Pharmaceutical Industry. On July 2010 Aptuit acquired the former GSK Medicine Research Centre in Verona (Italy) becoming a global leader in integrated pharmaceutical services, world class drug development and drug discovery solutions to speed the process from discovery to launch.