Therapeutic drug monitoring (TDM)

Requesting a blood level measurement of a drug is part of the global approach known as "Therapeutic Drug Monitoring". Diverse situations require this monitoring approach, such as inadequate response to treatment or organ failure. Every drug however does not possess all the characteristics for a TDM program. The therapeutic range of a TDM drug has indeed to be narrow and its interindividual pharmacokinetic variability to be wide. As the development of new drugs is currently slowing down, the precise management of existing treatments certainly deserves progress, but needs however to be applied rationally, starting from a valid indication to blood sampling, and ending with a sound dosage adaptation decision.

TDM is an important research area of our Division of Clinical Pharmacology and Toxicology. We are indeed interested in the evaluation of the utilization and of the clinical benefit of blood concentration monitoring of drugs in patients, in order to optimize their pharmacological treatment. This research is carried out both on a practical (i.e. R&D projects, clinical trials) and theoretical (i.e. PK/PD and TDM meta-analyses) basis. We are mainly working on anti-HIV and targeted anticancer drugs, but other drugs are also regularly evaluated (e.g. antivirals). This activity is performed in close link with the PK/PD modeling research activity of our Division.

Our Division is also in charge of providing clinical interpretations of routine drug levels performed in patients of the CHUV (and of Switzerland for some specific drugs). We are therefore performing practical research on the impact and the quality of this activity.

Research and Development

Our current R&D project is described on its dedicated page:

• Intelligent Integrated Systems for Personalized Medicine (ISyPeM)

Clinical trials

Here are also some additional information about our main ongoing clinical trial:

• Imatinib Concentration Monitoring Evaluation (I-COME)

Bibliography

Our principal recent publications on this research area are listed below. For publications on PK/PD relationship (related or not to TDM outcome), please refer to the dedicated pages.

Clinical research

• Gotta V, Widmer N, Montemurro M, Leyvraz S, Haouala A, Decosterd LA, Csajka C, Buclin T. Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels. Clin Pharmacokinet 2012; 51(3): 187-201. PMID: 22339450.
• Fayet Mello A, Buclin T, Decosterd LA, Delhumeau C, di Iulio J, Fleurent A, Schneider MP, Cavassini M, Telenti A, Hirschel B, Calmy A. Successful efavirenz dose reduction guided by therapeutic drug monitoring. Antivir Ther 2011;16(2):189-97. PMID: 21447868.
• Buclin T, Widmer N, Biollaz J, Decosterd LA. Who is in charge of assessing therapeutic drug monitoring? The case of imatinib. Lancet Oncol 2011;12(1): 9-11. PMID: 21111679.
• Widmer N, Gotta V, Haouala A, Decosterd LA. Tyrosine kinase inhibitors concentration monitoring in chronic myeloid leukemia. Leuk Res 2010;34(6):698-9. PMID: 20074797.
• Gotta V, Widmer N, Decosterd LA, Csajka C, Duchosal MA, Chalandon Y, Heim D, Gregor M, Buclin T. Therapeutisches Drug-Monitoring von Imatinib. Schweiz Med Forum 2010;10(23):403–406.

Engineering

• You W, Widmer N, De Micheli G. Example-based support vector machine for drug concentration analysis. Conf Proc IEEE Eng Med Biol Soc 2011;2011:153-7. PMID: 22254273.

PK/PD and TDM systematic reviews

• von Mehren M, Widmer N. Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): An emerging role for drug blood level testing? Cancer Treat Rev 2011;37(4):291-299. PMID: 21078547.
• Widmer N, Meylan P, Ivanyuk A, Aouri M, Decosterd LA, Buclin T. Oseltamivir in seasonal, avian H5N1 and pandemic 2009 A/H1N1 influenza: pharmacokinetic and pharmacodynamic characteristics. Clin Pharmacokinet 2010;49(11):741-65. PMID: 20923248.
• Perrottet N, Decosterd LA, Meylan P, Pascual M, Biollaz J, Buclin T. Valganciclovir in adult solid organ transplant recipients: pharmacokinetic and pharmacodynamic characteristics and clinical interpretation of plasma concentration measurements. Clin Pharmacokinet 2009;48(6):399-418. PMID: 19650679.

Practical research

• Fernandez S, Widmer N, Buclin T, Biollaz J, Csajka C. Evaluation of the impact of a therapeutic drug monitoring program in a Swiss University Hospital. In: ESCP-GSASA, 38th Symposium on Clinical Pharmacy, 30 years of clinical pharmacy: a bright future ahead. Pharm World Sci 2010;32(2)283-284. Web of Science.