|This month’s interview comes from Milan, Italy, from long-term member, colleague and friend Dr. Dario Cattaneo (who wins my vote for best dancer at the wonderful congress dinner at the St Laurence Cathedral in Rotterdam). Dario shares his experiences in the worlds of TDM for immunosuppressant and anti-infective drugs, and how recently these worlds have started to intertwine.
Laboratory of Pharmacokinetics, Clinical Pharmacology Unit
Luigi Sacco University Hospital, Milan, Italy
Photo: Dario and colleagues, IATDMCT Congress dinner, Rotterdam, 13/10/15
Can you tell us a little bit about your respective roles? What is a typical day like for you?
Since 2008 I have been the clinical pharmacologist in charge of the Laboratory of Pharmacokinetics (Clinical Pharmacology Unit, Luigi Sacco University Hospital, Milan, Italy). The Unit is a national reference center for the treatment of infectious diseases, with nearly 6000 HIV-infected patients in outpatient care. I am also an assistant professor of pharmacology at the Faculty of Medicine, University of Milan.
A typical working day is usually spent in the lab, involving clinical validation of exams (therapeutic drug monitoring by HPLC, mass spectrometry or immunoassays) provided by our Unit. I am also consulted as a clinical pharmacologist, working with physicians from different departments of our and other hospitals (mainly the departments of Infectious diseases, Pediatrics, Psychiatry and Intensive Care) for optimization of drug doses in atypical patients and/or in complex clinical scenarios. On most days I spend some time trying to explain to skeptical colleagues that TDM done by chromatographic methods is not only for research, but can be really useful in day-by-day clinical management of patients.
Is there anything that your laboratory does or that is done at your hospital that you would consider innovative?
I think that most innovative thing done in our lab is the routine application of TDM for a wide panel of drugs, including those that are not usually considered to have a narrow therapeutic index. We routinely measure nearly 80 molecules including antiepileptic drugs, antibiotics, antifungal agents, antiretrovirals, antidepressants and antipsychotic drugs. When appropriate, TDM analyses are combined with pharmacogenetic tests.
In Italy only a few hospitals provide TDM services within a broad pharmacology service; in a large majority of hospitals TDM is performed routinely for a very few molecules (immunosuppressive agents, some olds antiepileptic, digoxin and couple of antibiotics) and is carried out by the Microbiology or Pathology Laboratories (that do not have detailed knowledge on PK/TDM).
How did you become interested in your area of expertise?
After completing my degree in Pharmacy, in 1997 I successfully applied for a fellowship in a post-degree specialization course in clinical pharmacological research organized by the Mario Negri Institute for Pharmacological Research of Bergamo, directed by Prof. Giuseppe Remuzzi (past president of the International Society of Nephrology and worldwide opinion leader in the fields of chronic kidney diseases and organ transplantation). I spent the first three years of my fellowship in the Laboratory of Clinical Chemistry and pharmacokinetics, starting to become familiarized with the TDM of immunosuppressants, a “first love” that fully involved my working life , including the remaining years spent at the Mario Negri Institute in charge of the Clinical Pharmacology and Pharmacogentics Unit. In 2001 I started my PhD at the Open University, UK, supervised by Atholl Johnston who invited me to join the IATDMCT meeting in Basel, and to become a member.
During these years I had the opportunity to get to know and to share my research with opinion leaders in the fields of immunosuppressants such as Teun Van Gelder, Pierre Marquet, David Holt, Michael Oellerich and many others who have opened my mind and greatly helped me in designing clinical research primarily concerned with the PK/TDM/pharmacogenetics of cyclosporine and mycophenolic acid.
In 2008 I move from the Mario Negri Institute to the Luigi Sacco Hospital, where no organ transplants are routinely performed. I had to leave the exciting field of immunosuppressants and began working with anti-infecting agents. Interestingly, my last accepted publication deals with the TDM of antiretrovirals in HIV/HCV co-infected patients who underwent liver transplantations, which is a nice mix of my former and present research life.
Is there anything that you’ve seen elsewhere or heard about and thought “I’d like to incorporate that idea at my center”?
Five years ago I had the opportunity to visit the Pharmacology Unit of Limoges University Hospital, directed by Pierre Marquet. Besides the impressive skills, equipment and expertise I observed there, I would like to implement a similar service of Bayesian dose adaptation (such as PKJust, ISBA, etc) and apply it for the individualization of drug doses in critically ill patients.
What sort of research do you have on the horizon that you think might influence clinical practice in the future?
We are attempting to favor the implementation and possibly the widespread diffusion of TDM in the fields of pregnancy, neonatology and pediatrics, with the goal to maximize the effects of acute and/or chronic therapies in pediatric patients, limiting as much as we can the development of drug-related side effects in this fragile population. We are also attempting to perform pharmacoeconomic analysis with the goal to convince different stakeholders that TDM (eventually combined with pharmacogenetics) is cost-effective, allowing them to optimize available resources.
What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?
I envisage the future of TDM as an even more feasible tool for drug dose adaptation, considering the advent of technologies able to reliably measure drug concentrations at the bedside in real time, combined with specific software allowing dose adaptation considering individual clinical features (co-medications, liver kidney function, age, weight, volume distribution, etc). I agree with the proposal to change the meaning of the acronym TDM from therapeutic drug monitoring to therapeutic drug management.
The main challenges we face may be analytical (reduction in the turnaround times cannot be paid by a reduction in method performance) and clinical (it is important to prospectively demonstrated that such approaches are both cost-effective and associated with significant improvements in patient outcomes).
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