IN VIVO CARDIOVASCULAR STUDIES

CVS Safety Pharmacology defined in ICH S7A aims to assess the effects of a test substance on cardiovascular function whereas ICH S7B is focused on arrhythmogenic risk and QT prolongation.

In addition to the core battery, there are other cardiovascular risk factors, for which broad evaluation of hemodynamic parameters in anesthetized large animals is highly recommended. Depending on the effects observed during the core battery studies, or during phase 1 clinical studies, additional follow-up studies can be proposed.

Cardiovascular parameters:

- Arterial Blood Pressure (ABP, mmHg)
- Left Ventricular Pressure (mmHg)
- Heart Rate (HR, bpm)
- PR interval (ms)
- QRS interval (ms)
- QT and corrected QT

Examples of follow-up studies

> Hemodynamic evaluation in anesthetized dogs (intact or cardiac denervated models)

> Proarrythmia or pathophysiological models

> Orthostatic hypotension

> Pulmonary and renal hypertension

> Combined EEG and blood pressure in conscious rats