The research and development work of our Laboratory is in line with the interest of the Division of Clinical Pharmacology and Toxicology, now part of the Service of Biomedicine of the Centre Hospitalier Universitaire Vaudois (CHUV), our University Hospital at Lausanne, Switzerland. The Laboratory is active in the discipline of clinical pharmacology, which aims at getting better and more secure use of drugs by increasing our understanding of the existing link between pharmacokinetics / pharmacogenetics and the response (or absence of response) and/or the toxicity elicited by drug treatment.
During the last years, we have developed at CHUV a new capacity of technical tools (mass spectrometry facility, triple quadripole and linear trap instruments), massive and facilitated access to integrated pharmacology and genetics databases and have applied them to the domain of antiretrovirals, infectious diseases, oncology, and antimalarials therapy.
Access to high throughput analyses by tandem mass spectrometry has also become a necessity for many biomedical research programs at CHUV and collaborating Swiss academic centers. Our efforts have thus aimed at providing CHUV with efficient instruments of ultra and high performance liquid chromatography coupled to a triple quadripole tandem mass spectrometry (HPLC-MS/MS; UPLC-MS/ MS). This has allowed to respond efficiently to the increasing number of analytical demands from large scale clinical research programs in the field of pharmacogenetics and pharmacokinetics of current and new antiretrovirals and antimalarial combination treatments. Moreover, the Laboratory has been active in the setting-up of various high throughput multiplex assays for the Therapeutic Drugm Monitoring (TDM) of current and new classes of antiretrovirals, antifungals, antibiotics and anticancer targeted agents, as well as new antimalarial combinations regimens.
Clinical pharmacokinetic and pharmacogenetic research efforts have been particularly pursued in HIV therapeutics, targeted anticancer therapy and recent antimalarials combination treatment, because of the prevalence of toxicity, the life-long nature of treatment, and the complexity inherent to multidrug therapy.
Pharmacogenetics aim at determining patients’ genetic predisposition influencing drug exposure, toxicity and clinical response. Alternately, drug pharmacokinetics is the final phenotypic trait of patients drug’s exposure, influenced by complex genetic and non-genetic factors affecting drug transport and metabolism. In addition, since previous pharmacokinetics studies have almost exclusively focused only on the parent drug concentrations, the line of research developed in our laboratory aims at integrating also the patient’s drug metabolites profiles.
In conclusion, our research efforts aim overall at increasing the current understanding of the complex gene-environmental interplay influencing toxicity and efficacy of pharmacological treatments at the patient and the population levels, thus offering new possibilities for improving the long term tolerability and response to treatments.
PD Dr Laurent A. Decosterd, PhD
Privat Docent, Maître d'Enseignement et de Recherche, University of Lausanne,
Research Section Leader, Division of Clinical Pharmacology -Laboratory
Service of Biomedicine
BH18-Labo 218-226
Centre Hospitalier Universitaire Vaudois
CH-1011 LAUSANNE
Switzerland
Tel +41 21 31 44272
Bip : +41 79 556 54 13
Fax +41 21 31 48098
LaurentArthur.Decosterd@chuv.ch
Selected publications in the field of antimalarial treatment:
Hodel E M, Genton B, Zanolari B, Mercier T, Duong S, Beck H-P, Olliaro P, Decosterd LA, Ariey F. Residual antimalarials at admission in malaria patients from Cambodia – indication of drug pressure. J Infect Dis 202, 1088-1094 (2010).
Hodel E M, Kabanywanyi AM, Malila A, Zanolari B, Mercier T, Beck H-P, Olliaro P, Decosterd LA, Genton B. Residual antimalarials in malaria patients from Tanzania – implications on drug efficacy assessment and spread of parasite resistance. PlosOne 4 (12) e8184 (2009)
Keiser J, Gruyer MS, Perrottet N, Zanolari B, Mercier T, Decosterd LA. Pharmacokinetics parameters of martesunate and dihydroartemisinin in rats infected or not by Fasciola hepatica. J Antimicrob Chemother 63, 543-549 (2009).
Hodel EM, Zanolari B, Mercier T, Biollaz J, Keiser J, Olliaro P, Genton B, Decosterd LA. A single LC tandem MS method for the simultaneous determination of 14 antimalarials and metabolites in human plasma. J Chromatog B 877, 867–886 (2009)
