CORE BATTERY - REGULATORY PACKAGE

Porsolt's broad experience in general pharmacology makes us the ideal partner to conduct your Safety Pharmacology experiments.

Porsolt offers full GLP safety studies in both in vitro and in vivo models with facilities, procedures, materials, and software, that have been validated to GLP standards.

Regulatory Package ICH S7 | Central Nervous System studies

Porsolt regulatory package includes required Central Nervous System studies that investigate the effects of the test substance on the central nervous system. We provide evaluation on motor activity, behavioral changes, coordination, sensory/motor reflex responses and body temperature.

In addition we provide supplemental studies for behavioral pharmacology, learning and memory, neurobiology and electrophysiology.

Regulatory Package ICH S7 |Cardiovascular studies

We provides regulatory in vitro Cardiovascular studies : hERG & Purkinje assays.

While the hERG channel is still considered to be the main target for in vitro proarrhythmic risk assessment, a rapid and preliminary test of the L type calcium current (ICaL), the rapid component of the sodium current (INa) and the ionic currents responsible for maintaining resting membrane potential (the inward rectifier potassium current IK1) using the patch-clamp technique in transfected cells is recommended for drawing a more complete cardiac risk profile of a new drug.

Porsolt provides in vivo Cardiovascular studies in conscious or anesthetized animals to evaluate arrhythmogenic risk and QT prolongation.

In addition to the core battery, we offer supplemental to evaluate other cardiovascular risk factors as hemodynamic parameters in anesthetized large animals which are highly recommended.

Parameters in CONCIOUS ANIMALS (TELEMETRY)

     - Mean, systolic and diastolic aortic blood pressure
     - Left ventricular pressure
     - Heart rate
     - dP/dt max, min
     - Tension time index
     - PR interval
     - QT interval
     - Corrected QT interval

Parameters in ANESTHETIZED ANIMALS

     - Mean, systolic and diastolic aortic blood pressure
     - Left ventricular pressure, Left ventricular end diastolic blood pressure
     - Cardiac output
     - Renal blood flow (option: Left circumflex coronary artery blood flow and resistance)
     - Heart rate
     - Pulmonary artery blood pressure and Pulmonary capillary wedge pressure
     - dP/dt max, min
     - Total peripheral resistance
     - Index of arteriolar renal resistance
     - Stroke volume
     - Systolic ejection time
     - Tension time index
     - Left cardiac work
     - PR interval
     - QT interval
     - Corrected QT interval

Regulatory Package ICH S7 | Respiratory studies

Respiratory Safety Pharmacology as described in ICH S7A core battery aims to evaluate the effects of a test substance on pulmonary function.

The basic procedure uses whole body plethysmography.

Respiratory parameters:

- Inspiratory Time (Ti, ms)
- Expiratory Time (Te, ms)
- Peak Inspiratory Flow (PIF, ml/s)
- Peak Expiratory Flow (PEF, ml/s)
- Tidal Volume (TV, ml)
- Respiratory Rate (ResR, breaths/min)
- Relaxation Time (Tr, ms)
- Pause = (Te - Tr)/Tr
- Enhanced Pause (Penh) = Pause x PEF/PIF
- Minute volume (MV, ml/min) = (TV x ResR)

Several supplementary and follow-up studies can be designed to further evaluate the effects on respiratory function.

Regulatory guidance for Safety pharmacology studies for human pharmaceuticals

The primary reference document for safety pharmacology is ICH S7A , followed by and ICH S7B: 

ICH S7A: Safety pharmacology studies for human pharmaceuticals. >>

ICH S7B: Nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals. >>