Assistant Professor, School of Medicine
Rennes University Hospital, France
This month’s interview is one we did at the end of last year with Young Scientist Florian Lemaitre. Florian was awarded the best YS oral prize for his presentation concerning long-term follow up after monitoring of intracellular tacrolimus concentrations and pharmacodynamic biomarkers in liver transplant patients (see the December 2019 Compass). Florian had several excellent submissions at the congress and the YS committee actually had trouble deciding which piece of work to award! Keep an eye on this very promising member.
Given the current global scenario, we will take a break from the current blog format of member interviews. Future blog pieces will address how members are dealing with the impact of COVID-19 in their work.
Can you tell us a little bit about your respective roles? What is a typical day like for you?
I am an Assistant Professor in Pharmacology at the Rennes University Hospital, France. The Department is led by Prof. Eric Bellissant and has several units: clinical trials, biometry pharmacovigilance, pharmacoepidemiology, clinical investigation and biological pharmacology, the latter dedicated to Therapeutic Drug Monitoring (led by Prof. Marie-Clémence Verdier, also an IATDMCT member). I’m in charge of TDM of immunosuppressive drugs, the largest activity of our unit with more than 18,000 analyses conducted annually. I’m also responsible for antiretroviral TDM and am the pharmacologist of the regional multidisciplinary team dedicated to managing HIV patients. We have an original line concerned with the biological diagnosis of Alzheimer’s disease that I also lead.
Although TDM of immunosuppressive drugs is about half of our analyses annually, we perform TDM of other drugs with a tropism for anti-infectives, of which beta-lactams are an important part and our laboratory has a long history with its provision.
I try to find a balance between teaching activities at the School of Medicine, research in transplantation pharmacology and my duties as hospital practitioner in the pharmacology laboratory.
Is there anything that your laboratory does, or that is done at your centre, that you would consider innovative?
We recently applied a microsampling approach using volumetric absorptive devices for the TDM of immunosuppressive drugs. This was a collaboration involving IATDMCT colleagues from Erasmus Hospital in Rotterdam and Dr Camille Tron from our lab. We are using this approach for tacrolimus by determining AUCs in specific cases: patients exhibiting toxicity or rejection with trough concentrations within the therapeutic range. It is really helpful to explain things we were unable to understand before. I really think it is the future of TDM: why perform venepuncture when you can use a finger prick blood sample? It offers many opportunities, including at-home TDM for patients with chronic disease.
What technological innovations have entered into use during your career that have permitted a change, or evolution, in practice?
Liquid-chromatography tandem mass spectrometry is certainly the approach that has taken TDM forward. It allows multiplexing analysis and measuring very limited amounts of drugs in various matrices. The ongoing improvement in sensitivity of equipment allow us to quantitate new drugs with sub nanogram per millilitre levels in patients, such as tyrosine kinase inhibitors as well as measuring drugs directly in cells as we do in Rennes for tacrolimus. LC-MS/MS also permits measurement of therapeutic antibodies or protein biomarkers.
How did you become interested in your area of expertise?
I would say by accident! As a resident at the Rennes University Hospital, I opted to move to the Poitiers University Hospital for personal motives. When I had to choose my next traineeship, a colleague suggested I change my initial choice to a rotation in the pharmacology/toxicology laboratory, as he had a project he wanted to complete. I did not regret that decision! Dr Nicolas Venisse, current chair of the environmental toxicology committee of the IATDMCT, gave me a taste of being a pharmacologist. At the time, I was passionate about antibiotic pharmacology, which remains my second hobby. I then joined Robert Farinotti’s team as an Assistant at the laboratory unit of the Pharmacy Department of Pitié-Salpêtrière Hospital in Paris. They perform the greatest number of heart transplantations in France, so I had good training in immunosuppressive drug TDM with very experienced clinical teams interacting with our department.
I then had the opportunity to undertake my PhD under the supervision of Prof. Christine Fernandez and during this period I learned a lot in pharmacokinetics and basic science. The topic was optimization of immunosuppressive treatments and, today, this is still my area of research.
Is there anything that you’ve seen or heard about recently and thought “I’d like to incorporate that idea at my centre”?
Through attending IATDMCT meetings, I have seen and been impressed by the implementation of modelling in clinical practice. I definitely think we should develop and incorporate it in our processes our department. There are now many software solutions available and, even for non-specialists, they allow improving dose adjustments. It really helps early attainment of target concentrations particularly in special populations, such as intensive care patients, and may refine our estimation of trough concentrations in patients with multiple samples. This makes TDM very flexible and helps working beyond restrictive trough concentration measurements.
What sort of research do you have on the horizon that you think might influence clinical practice in the future?
We are dedicated to the improvement of transplant care and we think there are other pharmacological approaches that better reflect immunosuppressive drug effect than trough whole blood concentration measurements. We cannot consider the actual situation as an acceptable goal: there is still a room for improvement. We have therefore developed several new drug monitoring approaches, in addition to measuring intracellular concentrations, including measuring concentrations in bile or in endomyocardial biopsies. We believe these new approaches may at least help explore the complex interplay between patient, drug and outcome. Several teams have worked on similar developments within the IATDMCT immunosuppressive drugs committee and we have to work together to provide an answer to this research question.
Our final objective is to develop new methods to predict and decrease graft rejection, new approaches that avoid biopsies, decreasing adverse events, increasing graft and patient survival as well as quality of life.
What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?
I do think we are currently at a turning point. There are areas of interest for pharmacologists, such as the exciting field of tyrosine kinase inhibitors, however the most recently developed drugs typically present reduced pharmacokinetic variability, high efficacy and fewer drug-drug interactions. The pharmacologist’s expertise might be challenged by this situation. However, I do see two very interesting developments for the profession: I already mentioned the rising of microsampling TDM. It represents a unique opportunity to re-evaluate the exposure-response relationship of drugs using new generation volumetric devices due to the ease of access to multiple samples permitting AUC determination.
The other area we should develop is pharmacodynamics. Several biomarkers of treatment effect have been explored and I think it may be an immense field of possibilities located at the frontier of different scientific domains. Most biomarkers are peptides or proteins, so developing adapted analytical methods is a requirement. I think it’s a great chance for pharmacologists and we should jump at the opportunity.
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