Jacques Turgeon, BPharm, PhD, and Veronique Michaud, BPharm, PhD, are respectively Chief Executive Officer and Chief Operating Officer of the Tabula Rasa Healthcare (TRHC) Precision Pharmacotherapy Research and Development Institute. The Institute is committed to the development of TRHC’s proprietary products, including their validation and recognition by the scientific and regulatory communities, to optimize medication regimens in order to improve patient outcomes, reduce utilization of various healthcare services, lower healthcare costs, and manage risk. The Institute is based in the Lake Nona Medical City in Orlando, Florida.
Jacques Turgeon, BPharm, PhD
Dr. Turgeon is recognized internationally for his excellence in research and pharmacy education. He has received more than $70 million in research awards and authored more than 130 peer-reviewed articles. Dr. Turgeon obtained his Baccalaureate degree in pharmacy (BPharm), MSc in pharmacokinetics, and PhD in drug metabolism from Laval University, Quebec City, Quebec, Canada.
In the early 1980s, only two isoforms of the cytochrome P450 system were known. Dr. Turgeon’s PhD thesis reported, for the first time, that at least seven isoforms of the cytochrome P450 system should exist and were required to metabolize the Class 1b antiarrhythmic and probe drug substrate mexiletine. These important observations led to the discovery of several other cytochrome P450 isoforms by several laboratories worldwide. He then undertook post-doctoral studies in the Department of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee, under the supervision of Dr. Dan M. Roden. His studies focused on pharmacogenomics, drug-drug interactions, and the electrophysiological properties of drugs, with a special interest in potassium channel blockers and drug-induced Long QT Syndrome (LQTS).
Dr. Turgeon established his laboratory in Quebec City in 1990. Shortly after, he reported on the role of a specific isoform of the cytochrome P450 system, CYP2D6, on the metabolism of several antiarrhythmic drugs (mexiletine, encainide, flecainide, propafenone, procainamide, quinidine [inhibitor]) and other pharmacological classes of drugs (venlafaxine, fluoxetine, diphenydramine). He conducted in vitro metabolism studies, pharmacokinetics and pharmacogenomics studies in healthy volunteers and patients, and clinical studies in patients with cardiac arrhythmias. Using purified cytochrome P450 isozymes, he characterized the involvement of known isoforms on the metabolism of a several drugs leading to the development of the first example of drug-drug interaction tables based on cytochrome P450 enzymes.
Such research led to collaboration with pharmaceutical companies interested in understanding, predicting, and preventing drug-drug interactions. The international pharmaceutical company, Bayer, approached Dr. Turgeon to use his tool to educate pharmacists and physicians for use in preventing drug-drug interactions. Bayer was introducing a new lipid lowering drug, cerivastatin, to the market with a distinct drug metabolism profile compared to other drugs of the same class. By conducting a literature search and generating data in his laboratory, Dr. Turgeon was able to significantly extent the table of cytochrome P450 isoform substrates, inhibitors, and inducers. He developed the table using the notion of competitive inhibition as the core element of this concept. He classified each drug on the market under specific isoforms involved in its metabolism and characterized the affinity of the substrates (low, medium, and high affinity) for each enzyme. This extensive work, which led to the creation of a spin-off company, InterMed-Rx®, in 2005 (acquired by TRHC in 2015), is the basis for TRHC’s proprietary competitive-inhibition, accumulative multi-drug interaction science which is now available and incorporated in TRHC’s Medication Risk Mitigation Matrix®.
In addition to the comprehensive mapping of cytochrome P450 isoforms, the laboratory’s second major topic of interest was the study of drug-induced LQTS. Some of the work he performed during his post-doctoral studies culminated with the identification of the blocker of the slow component of the delayed rectifier potassium channel (IKs) namely, indapamide. Using patch-clamp techniques and isolated perfused hearts, he was able to identify 13 other drugs with potassium channel blocking properties. These drugs were then either removed from the market or associated with a Black Box warning as a result of his work. The most notable example is the demonstration that the prokinetic agent, cisapride, is one of the most potent potassium channel blocker ever put on the market. Dr. Turgeon was involved as an expert in international legal lawsuits associated with death observed in patients treated with cisapride.
Dr. Turgeon moved to Montreal to become Senior Director of a contractual research organization (CRO) where he performed more than 300 pharmacokinetics, drug-drug interaction, and bioequivalence studies for two years. In June 2000, he became Dean, Faculty of Pharmacy, Université de Montréal, where for five years he played a vital role in the development of pharmacy in the province of Quebec; created the first Entry Level PharmD program in Canada, a BSc degree in pharmaceutical science; and led the construction of a new building for the Faculty, the Jean et Coutu’s Pavilion.
Veronique Michaud, BPharm, MSc, PhD
In 2000, Dr. Veronique Michaud joined Dr. Turgeon’s laboratory in Montreal as a MSc/PhD student. She had just completed a BPharm degree from Laval University where Dr. Turgeon was a professor. Her training consisted of performing pharmacokinetic studies in healthy volunteers and patients, studying pharmacogenomics, and involvement in the characterization of drug metabolism in extra-hepatic tissues. At the time, her most prominent publication was the characterization of cytochrome P450 isoforms in the human heart. No other laboratory had been able to collect samples from a large group of patients (n=82), prepare microsomes retaining cytochrome P450 activities from frozen tissues, and demonstrate the involvement of various isoforms, especially CYP2J2, in the metabolism of drugs in human heart. As part of Dr. Turgeon’s team, she played a vital role in the development of cytochrome P450 isoform tables. They collaborated in the development of InterMed-Rx®, which evolved from a simple table to a website, and finally a clinical decision support system implemented by community pharmacies and hospitals.
Following the completion of her PhD in 2010, she undertook post-doctoral studies at McGill University, researching the pharmacogenomics of HIV drugs. She worked under the supervision of researcher Dr. Mark Weinberg, who was previously involved in the discovery of 3-TC. After a one-year post-doctorate, she accepted a second post-doctoral position and joined Dr. David Flockhart in the Department of Clinical Pharmacology, Indiana University, where she established international collaboration and published a landmark review in the prestigious journal Pharmacological Reviews.
In 2012, she returned to Université de Montréal as assistant professor, Faculty of Pharmacy. She was also a researcher at the Centre de Recherche, du Centre Hospitalier de l’Université de Montréal (CRCHUM), where she established her own laboratory. So far during her career, she has earned more than $22 million in research awards and published more than 30 peer-reviewed journal articles.
After her post-doctoral studies, she re-established collaboration with Dr. Turgeon and they collaborated on several original studies in pharmacogenomics and drug-drug interactions, with Dr. Michaud leading most studies. The most significant studies conducted at this time examined drug metabolism in various human tissues, the impact of disease-state on cytochrome P450 activities, and the role of drug transporters in the disposition of drugs.
As they performed innovative research, they also maintained their involvement with the development of InterMed-Rx which had then achieved the status of a Clinical Decision Support System. The software was implemented in more than 200 community pharmacies (Familiprix and Walmart community pharmacies) in three provinces, and in more than ten hospitals. In particular, level 4 university hospitals such as the Institut de Gériatrie de l’Université de Montréal and the psychiatric Institut Hôpital Louis-H. Lafontaine in Montréal.
In September 2015, TRHC acquired InterMed-Rx® and Dr. Turgeon became Chief Scientific Officer of the company. Dr. Michaud then joined TRHC in September 2016, when the company was introduced to the public market at the NASDAQ. In 2018, they were recruited at the College of Pharmacy, University of Florida, as Associate Dean, Lake Nona Campus, and Associate Professor, Department of Pharmacotherapy and Translational Research. They established several collaborations with academic and industrial partners in Lake Nona Medical City during 2018, and rejoined TRHC to create the Institute in January 2019.