CV Science

Pierre Marquet MD, PhD transplantation pharmacology

Course and current status

Pierre MARQUET has been a Doctor of Medicine since 1986 and obtained a master in statistics and epidemiology followed by a PhD in physiology in 1992. After several years as a hospital pharmacologist at Limoges University Hospital, he has been an associate professor of pharmacology since 1998 and in 2001, became a full professor at the Faculty of Medicine of Limoges, France. Pierre Marquet is currently:

• Head of the “Pharmacology, Toxicology and Pharmacovigilance” Department at the University Hospital of Limoges.
• Director of the INSERM U850 research unit called “Pharmacology of immunosuppressive drugs in transplantation” (INSERM is the French Institute of Medical and Health Research).
• Vice-President of the board of Directors of University Hospital of Limoges, in charge of research
• President-elect of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT)
• Member of the council of the French Society of Pharmacology and Therapeutics (SFPT)
• Coordinator of the “drugs and pharmacology” working group of the French-speaking Society of Transplantation (SFT)
• Member of several scientific committees
• Member of the editorial board of Therapeutic Drug Monitoring since 2002, International Journal of Clinical Pharmacology since 2004 and Pharmacological Research since 2008.

 Pierre Marquet received the following awards:

• Young Scientist Award of the French Society of Analytical Toxicology, 1995.
• Young Investigator Award of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology, Washington, September 2001.
• C.E. Pippenger Award for outstanding contributions to TDM, presented by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology, Montreal, October 2009.

INSERM UMR-S850 « Pharmacology of immunosuppressants in transplantation » is a research unit created in 2007 and jointly supported by INSERM and the University of Limoges, also with a strong partnership with the University Hospital of Limoges, France.

It is housed at the medical school (for its basic and experimental research) and at the University Hospital (for its clinical research).

The unit comprizes 9 teachers-researchers, 4 other MDs from the University Hospital, 1 or 2 post-doc, a minimum of 5 phD students and 6 engineers, technicians or administrative personnels.

Scientific summary

Pierre Marquet conducts translational research on treatment personalization, mainly concerning immunosuppressants (IS) in organ transplantation, which covers: new analytical methodologies for IS; metabolic and pharmacogenetic studies of the IS; application to population pharmacogenetic-pharmacokinetic analysis and therapeutic drug monitoring; and epidemiological studies and clinical trials in transplant patients.

He has published over 180 papers in peer-reviewed, international journals. 

The UMR-S850 carries out translational pharmacological research in transplantation with the aim:

• of identifying the factors of variability in the response and the toxicity of immunosuppressant drugs (IS), so as
• to propose individualised therapeutic strategies for transplanted patients in order to improve the long term survival of the transplanted organ and of the patients
• to clinically validate these strategies
• and to study their health and economical impacts in the mid and long term.

Since 2008, the unit has been studying in vivo the mechanism of the nephrotoxicity of calcineurin inhibitors (cyclosporine and tacrolimus), in particular on the cytoskeleton of the proximal renal tubular cell.  

They have developed and published a technological approach for the research on a large scale (“screening”) of precocious urine biomarkers of acute rejection or interstitial fibrosis/tubular atrophy, based on nano-HPLC coupled with mass spectrometry (MALDI-TOF/TOF).  

Since 2007, the unit has carried out a coherent set of in vivo studies of the implication of genetic polymorphisms in the metabolic enzymes and transport proteins in the pharmacokinetic variability of IS, with clinical confirmation (or in vitro confirmation of clinical hypotheses), whenever possible. A new research project concerning the influence of the polymorphisms of IS target proteins and their signaling pathways has begun.

They have developed innovative models and carried out extensive pharmacokinetic modelling of the major marketed IS in different transplantation types or auto-immune diseases, by individual and population approaches in parallel. The Bayesian estimators derived from these two approaches are jointly used in the expert system ExpertIS via the website ABIS/ISBA (https://pharmaco.chu-limoges.fr/) so as to secure the Bayesian estimation of AUC and the calculation of the recommended dose. Moreover, the population approach has allowed the team to identify or confirm the biological or genetic characteristics significantly influencing the PK of IS and useful to be taken into account in the calculation of the dose convenient to each patient by the Bayesian method. In particular, the pharmacogenetic characteristics have been taken into consideration in the form of diverse models of genetic effects.

The clinical transfer of these tools via the ABIS/ISBA website is increasingly successful with many transplantation centres, from France and abroad, sending requests. These tools (PK models and Bayesian estimators) are also used in the unit’s clinical trials or for other French and foreign investigators, both academic and industrial, whose aim is either to validate the individual dose adjustment approach or to test treatment optimization strategies with a diminution of the exposure to toxic IS under the cover of fine dose individualisation.

The INSERM UMR-S850 unit is also developing a programme of pharmaco-epidemiological studies in renal transplantation, whose aim is to identify predictive factors of the transplanted organ and recipient survival in the long term in real-life situations.