Posts Tagged ‘Preclinical Services’

How to Conserve Test Article, Time and Money with Telemetry

Posted by CorDynamics on March 11th, 2014

Here’s a familiar dilemma. Your research team detects unanticipated cardiovascular activity in your lead candidate but there is limited test article for follow-up discovery and safety studies.

In these cases, we often suggest either conscious telemetry or an anesthetized preparation in the guinea pig as an effective model for cardiovascular testing, when appropriate. Since they are smaller in size, guinea pigs can serve as a viable species when compound supply is limited.

In some cases, the guinea pig can use five times less compound to conduct studies than amounts needed for their larger counterparts, such as rabbits.

The Conscious Model

Using telemetry to deliver quasi beat-to-beat data, this guinea pig model generates ultra high fidelity QT interval correction. View Conscious Validation Data

The Anesthetized Model

In this preparation, we employ a well-characterized anesthetized method to screen for cardiovascular effects early. Cardiovascular parameters such as blood pressure, heart rate, as well as ECG are measured and cardiac functional assessments can also be provided. View Anesthetized Validation Data

While a plus in terms of compound conservation, the guinea pig’s small size and inherent anatomical obstacles do pose potential roadblocks. This is especially true in the hands of less experienced technical personnel. Guinea pigs have rather obscure vascular access due to the lack of a tail and their orogastric structure can make orally dosing somewhat challenging.

Although the guinea pig is not appropriate for every situation, with careful planning and expert execution, this species does indeed play a valuable role in the successful de-risking funnels employed by a number of our biopharmaceutical clients.

Filed under: Drug Discovery Services, Drug Safety Services, Telemetry | No Comments

CorDynamics to Showcase Cardiovascular Capabilities at SPS 2013

Posted by CorDynamics on September 10th, 2013

CorDynamics heads to Rotterdam for the Safety Pharmacology Society meeting next week, September 16-19th.

Peter Senese, CorDynamics co-founder and chief operating officer, along with Dr. Franz Hock, our European business developer will be on hand in The Netherlands to discuss cardiovascular safety assessments and capabilities:

• Telemetry—dual pressure, respiratory parameters, ECG

• Isolated Langendorff heart

• Electrophysiology, hemodynamics

Of special note, we will also be featuring the latest industry primer: Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays co-edited by Dr. Franz Hock.Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

Among a number of hot topics, the book argues the days of sequential drug development should be a thing of the past, replaced instead with simultaneous data generation combining toxicological, pharmacodynamic and pharmacokinetic data both from a preclinical and clinical environment.

To discuss these topics and more, please stop by our booth. If you’re not attending this year, feel free to contact us for more information.

 

Filed under: Drug Safety Services, Electrophysiology, Hemodynamics, Langendorff Heart, Telemetry | No Comments

Simultaneous Data Generation Connects Early Data to the Clinic

Posted by CorDynamics on May 22nd, 2013

Safety aspects have increasingly become an outstanding issue in the drug discovery and development arena with the FDA and the EMEA placing a clear emphasis on their importance.

The point is illustrated in the book Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, co-authored by Dr. Franz Hock, CorDynamics European Business Development Director.

Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

Sequential Development: The Paradigm of the Past

Up until 15 years ago, drug discovery and evaluation was a single, sequential process starting with the selection of the most active compound from a series of newly synthesized agents by means of special pharmacological assays.

• Safety aspects were addressed by pharmacological testing of the selected compound in high doses in assays directed at targets other than the intended indication of the new compound.

• These tests were followed by pharmacokinetic studies, which were mainly aimed at confirming a suitable half-life and oral activity.

• Safety aspects relied mostly on toxicity studies, which however gave information on changes of organ structure rather than on organ function.

• Toxicological and pharmacokinetic studies were adapted to the progress of studies in clinical pharmacology and clinical trials.

Simultaneous Data Generation: Today’s Paradigm

The sequential way of working has been replaced by simultaneous generation of data.

• Concurrent safety, pharmacodynamic and pharmacokinetic data is generated.

• If need be, bench-to-bedside and bedside-to-bench approaches can be facilitated to connect preclinical and clinical data as early as possible.

• Rather than a separation into toxicology, pharmacokinetics and clinical applications, a connectivity between all these disciplines is embraced.

This new paradigm is seen as mandatory in the eyes of regulatory bodies as well as among academic thought-leaders and drug development executives.

The industry as a whole has come to understand there is no real safety evaluation possible without combining toxicological, pharmacodynamic and pharmacokinetic data both from a preclinical and from a clinical environment.

To learn more on the topic or to order Dr. Hock’s book, click here.

 

Filed under: About Us, Drug Discovery Services, Drug Safety Services, Preclinical Consulting Services | No Comments

Ischemia/Reperfusion Model Provides Better Road Map for Biological Pathway

Posted by CorDynamics on January 22nd, 2013

Over the years, we’ve worked with clients to investigate potential treatments for myocardial ischemia/reperfusion injury. The challenge: biological processes associated with infarction and reperfusion injury are complicated and historically it’s been difficult to develop drugs that successfully salvage tissue damaged during a heart attack.

Our laboratory has released data demonstrating the reduction of myocardial infarct size in rats using one of our “gold-standard” small-animal preclinical models. In these rats, we produce cardiac ischemic damage to help clients study therapies that may reduce the amount of injured tissue resulting from a heart attack.

Ischemia/Reperfusion: Effect of nor-NOHA on MyCordial Injury

View Data

Briefly, we dosed rats with either vehicle or 100 mg/kg nor-NOHA (a selective arginase inhibitor) at 15 minutes prior to ligation of the left coronary artery. Following 30 minutes of myocardial ischemia, reperfusion was initiated and monitored for 2 hours. After 2 hours, infarct size was measured.

Models like this provide a better understanding of the biological pathways associated with reperfusion injury. In this case, the pathway of interest involves nitric oxide. With this knowledge in hand, a number of our clients are taking another look at the compounds in their arsenals in an effort to continue to refine them to address this critical therapeutic area.

Off the Beaten Path…

Our learnings from reperfusion injury are also being applied to other acute and chronic inflammatory conditions. Because reperfusion injury involves the inflammatory response, many types of compounds can be studied in this model to learn more about their effectiveness in a variety of conditions.

Filed under: Drug Discovery Services, Ischemia Reperfusion Models | No Comments

CorDynamics Sets Drug Discovery and Development 2013 Trade Show Calendar

Posted by Theresa Gralinski, Marketing Director at CorDynamics on December 19th, 2012

The CorDynamics team is saying goodbye to a great 2012 and looking forward to more research and collaboration with colleagues in 2013. Closing one calendar and turning to a new one, some of the first dates to fill in are our trade show exhibitions.

As we continue to grow the early-stage drug discovery side of our business, we will again be visiting the Experimental Biology meeting in Boston, April 20-24. I look forward to attending this event and meeting with colleagues focused on linking drug discovery to development.

In addition to EB, we’ll also be exhibiting at SOT, SPS and ACT.

  • Society of Toxicology 52nd Annual Meeting

San Antonio, Texas March 10-14

  • 2013 Safety Pharmacology Society Annual Meeting

Rotterdam, The Netherlands September 16-19

  • American College of Toxicology 34th Annual Meeting

San Antonio, Texas November 3-6

If you’re going to be at any of these meetings, please put us on your calendar.

Wishing you a very Healthy and Happy New Year.

Theresa Gralinski, Marketing Director

Filed under: Drug Safety Services | No Comments

Drug Discovery Generates Good Science, Business and Drug Development

Posted by Theresa Gralinski, Marketing Director at CorDynamics on August 08th, 2012

In my mind, the pharmaceutical and biotech industry can be reduced down to one elegant equation: good science + good business decisions = good drug development.

Good Science.
As the marketing director for CorDynamics, I spend a lot of my time discussing our innovative preclinical cardiovascular drug discovery and drug safety models. It’s our reason for being. My job is to communicate our capabilities and the good science we generate to clients, colleagues and potential customers.

Good Science=Good Business Decisions
As a member of the Healthcare Business Women’s—Chicago Chapter I’ve attended a number meetings led by dynamic senior healthcare and pharmaceutical executives discussing how to navigate our changing industry.

After each of these events, my underlying takeaway is that tough business decisions can be made easier when armed with good science.

When the science is solid and reliable—in our case from a cardiovascular drug discovery and drug safety side—it can be a useful guide for folks faced with extreme budget and timeline constraints.

It’s our job as the cardiovascular CRO, to understand the pressures on our clients as well as the need to be flexible, affordable and most importantly, collaborative in the work outsourced to us.

Good Science + Good Business Decisions = Good Drug Development
Earlier this year, I flew 2,000 miles to be with an aging parent undergoing surgery. I tried not to think of all the science, education and yes, business decisions that would go into this one procedure. All went well. As I headed to the pharmacy to pick up the prescriptions necessary to inspire a full recovery and greater wellness, I walked away with tangible proof of my theory.

Filed under: Drug Discovery Services, Drug Safety Services | No Comments

Preclinical Services Published in British Journal of Pharmacology

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on May 15th, 2012

When you have all the pieces of a puzzle, you get a clear picture.

Putting all the pieces together—CorDynamics leveraged our preclinical services to co-publish a paper in the British Journal of Pharmacology.

CorDynamics Preclinical Services

Collaboration
In collaboration with sponsor Hoffmann-La Roche, CorDynamics conducted both anesthetized canine and non-human primate telemetry studies to determine the molecular mechanism of cardiac arrhythmias observed during the course of a routine preclinical toxicology assessment.

Collaboration + Comprehensive Preclinical Studies
The compound RO5657, a CCR5 antagonist, had induced torsades de pointes (a life threatening cardiac arrhythmia) in normal, healthy animals. Employing a variety of preclinical cardiovascular models, the article investigated how and why a small-molecule compound exhibited cardiac side effects and torsades de pointes during preclinical toxicology studies.

The sponsor came to us to discuss the issues and contracted us to perform both anesthetized canine and non-human primate cardiovascular telemetry studies. The project became a textbook case of collaboration and integration.

Here’s the deal: when conducting screening studies of compounds on ion channels or isolated Langendorff hearts, you often don’t have the luxury to examine the other general toxicology study results concurrently. In this case, once all the studies were completed, we were able to confer and put them into perspective.

In fact, the ion channel and isolated heart interrogations ultimately predicted the anesthetized, telemetry and toxicology study results.

Collaboration + Comprehensive Preclinical Studies = Integrated Risk Assessment

This article confirms the importance of collaborating, taking the information garnered from a variety of safety pharmacology and preclinical toxicology models, and compiling the results to produce an integrated cardiovascular risk assessment.

This type of approach is vital to making rationale project decisions—and ultimately getting a clear, complete picture.

Filed under: Anesthetized Models, Cardiac Ion Channels, Drug Safety Services, Langendorff Heart, Preclinical Consulting Services, Telemetry | No Comments