NT-proBNP as a biomarker for the assessment of a potential cardiovascular drug-induced liability in beagle dogs.

The amino-terminal pro-brain natriuretic peptide (NT-proBNP) is released into the plasma predominantly from ventricular cardiomyocytes, particularly in patients with chronic cardiac diseases, although small amounts are detectable in the plasma of healthy subjects. While NT-proBNP has been widely exploited in human medicine, limited literature is available related to its characterization in veterinary medicine (e.g.

Characterisation of rodent dobutamine echocardiography for preclinical safety pharmacology assessment.

Introduction: Dobutamine stress echocardiography (DSE) is performed to detect subtle ischemic regions in the myocardium in patients suffering from stenosed coronary artery disease. While in a clinical and veterinary context DSE is performed daily, in the preclinical context, a very limited application has been described in the literature. In the drug development process, the safety of new chemical entities on the cardiovascular system is a primary requirement for the development of new agents/drugs for administration in humans.

A novel and integrated approach for the identification and characterization of drug-induced cardiac toxicity in the dog.

Cardiovascular toxicity represents one of the major reasons for the termination of the development of drugs, even in late development phases. This growing issue is often not restricted to specific therapeutic areas, and it is gaining critical importance, in particular for chronically administered drugs, highlighting the limitations in terms of sensitivity of the current investigational paradigms. Furthermore, drug-related changes may become evident after long-term administration for different reasons, including accumulation of the drug in the heart.

An integrated cardiovascular and neurobehavioural functional assessment in the conscious telemetered cynomolgus monkey.

Introduction: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. The purpose of this study was to validate, in the monkey, a model that incorporates the neurobehavioural assessment into the Safety Pharmacology cardiovascular study, allowing for an integrated evaluation of these two physiological systems.

Methods: Conscious male cynomolgus (Macaca fascicularis) monkeys (n=4) were given single oral doses of vehicle, D-amphetamine (0.

An improved method of electrode placement in configuration Lead II for the reliable ECG recording by telemetry in the conscious rat.

Introduction: Telemetry represents the gold standard technique for the acquisition of animal haemodynamic signals in the pharmaceutical preclinical development of new chemical entities. In terms of electrocardiographic signal recording, the quality is well established in large animals, mainly dog, non human primates and minipig, whereas it is still lacking in terms of satisfactory results in rodents (mouse and rat in particular). In very recent times, an increasing interest in early safety prediction for the reduction of cardiovascular attrition has been raised in all the major pharmaceutical companies, focusing in particular, on in vivo models.

An optimised neurobehavioural observation battery integrated with the assessment of cardiovascular function in the beagle dog.

Introduction: The objective of this study was to describe an optimised neurobehavioural observation battery in the beagle dog and to demonstrate that it can be used for an integrated assessment of cardiovascular and neurobehavioural functions within a single Safety Pharmacology study.

Methods: A standardised and detailed observation battery was established based on the direct examination of 44 signs, including behavioural responses and a full, systematic neurological examination, using clearly defined numerical scores. To complete the neurobehavioural assessment the remote observation of animals by video recording was also performed.

A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs.

Introduction: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry.

Methods: Conscious male beagle dogs (n=4) were given single oral doses of vehicle, and D-amphetamine (0.