CardioPulmonary and Safety Pharmacology


 
LRRI has the capability of performing safety pharmacology studies utilizing all routes of administration, including instillation and inhalation.  Cardiopulmonary safety pharmacology (CPSP) addresses both the FDA-required studies for safety pharmacology (GLP studies), as well as assessing early safety and disease models for basic research.  CPSP integrates best practices in pharmacology, physiology, and toxicology to identify adverse effects of drug candidates in preclinical studies and basic research aspects of disease models such as pulmonary hypertension.
 

 

CPSP capabilities include telemetry, plethysmography, ultrasound, several in vitro assays including vascular or bronchial ring or isolated lung assays, as well as molecular biology tools to investigate cardiovascular and respiratory disease models, and better understand the mechanism(s) of the disease.  CPSP also investigates the cardiovascular and pulmonary physiological effects and safety of new compounds developed by our pharmaceutical clients. 

 

CPSP’s telemetry capability includes four ITS telemetry (GLP), three DSI/Ponemah, and one DSI/EMKA (GLP) acquisition systems.  CPSP is aligned with investigators in Infectious diseases, as telemetry has proven to be an especially powerful tool in providing accurate information regarding the effects of infectious agents and the efficacy of applied therapies.  CPSP is also aligned with investigators in COPD, asthma, toxicology, and chemical exposure.  

Key Capabilities:

Cardiovascular

In Vivo:

Ultrasound/Echocardiography:  Rodent, Ferret, Rabbit, Dog/NHP

Small Animal Telemetry (DSI):  Mouse, Rat, Ferret, Rabbit

Large Animal telemetry (DSI): Dog and NHP

Large Animal Telemetry (ITS): NHP standard telemetry parameters: blood pressure and heart rate, ECG assessment (QRS duration and PR, RR, QT/QTc and arrhythmia assessment)

 

In Vitro: Vascular ring function

 

Cellular:  Western blots, RT-PCR, Northern/Southern gels, In situ zymography, cryosectioning for IHC staining, double immunofluorescence, specialty stains

Respiratory

In Vivo:

Traditional Restrained/Anesthetized Plethysmography in rodent (FlexiVent) and non-rodent species:  respiratory mechanics, forced maneuvers, quasistatic maneuvers, lung diffusion capacity, airway challenges

Unrestrained Whole Body Plethysmography in rodents or guinea pigs (EMKA Technologies; GLP): respiratory rate, volume, penH, inspiratory and expiratory times, apnea

 

In Vitro: Bronchial ring function and isolated lung function

 

Chemistry (Tier II: arterial blood gas analysis):  iSTAT and Siemens Rapidpoint 405 analyzer for laboratory testing of blood gases, electrolytes, metabolites, total hemoglobin, and hemoglobin derivatives in arterial, venous, and capillary whole blood samples.

Central Nervous System

Rodent Functional Observational Battery (FOB)

Startle Reflex

Chemical Withdrawal Assessment

 

ACCESS LRRI PUBLICATIONS ON THIS TOPIC IN PUBMED

 

Supportive Links:

 

Safety Pharmacology Society  http://www.safetypharmacology.org/

 

Society of Toxicology  http://www.toxicology.org/

 

ICHS7A guidelines Safety Pharmacology

 

ICHS7B guidelines Safety Pharmacology

 

January 2010  Guidance   Assessment of Abuse Potential of Drugs

 

ICHS6 guidelines Biotechnology-Derived Pharmaceuticals

 

ICHS4A  guidelines  Chronic Toxicity Testing

 

ICHS9  guidance  Nonclinical Evaluation for Anticancer Pharmaceuticals