In vitro tests for predicting drug-drug interactions: the need for validated procedures.
Over the past decade, the prediction of drug-drug interactions from in vitro studies has become a rapidly expanding field of research. Numerous papers and excellent review articles (Bertz & Granneman 1997; Ito et al. 1998a & b; Lin 2000; Bachmann & Ghosh 2001; Ekins & Wrighton 2001; Weaver 2001) have been published in this area. Yet like any new and fast-growing subject, this one has been developing with some confusion and without any real, efficient organisation. Depending on the drug tested, the models and extrapolation parameters used, etc., results and conclusions may vary widely from study to study (von Moltke et al. 1998; Weaver 2001). Several authors have called for validation of these procedures (Rodrigues et al. 2001; Kummar & Surapaneni 2001; Pelkonen et al. 2001a & b; Kremers 2002), and regulatory authorities intend to require better traceability and reliability (FDA & EMEA guidelines). A systematic and reliable approach is needed also to allow such protocols to be incorporated into early screening for potential drugs and new chemical entities. There is certainly a great need to standardise these studies and to verify their conclusions, but is true validation possible in this field? The main purpose of the present paper is to discuss this issue and to examine what is possible and what is needed to improve the quality of predictions made from in vitro experiments.
Kremers
Pierre
P
Advanced Technology Corporation, University Hospital (CHU), Institute of Pathology, B23, University of Liège, B-4000 Sart Tilman, Belgium. pkremers@ulg.ac.be
D019411:Clinical Laboratory Techniques / Q000592:standards*; D002986:Clinical Trials as Topic / Q000379:methods; D015195:Drug Design; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D006801:Humans; D066298:In Vitro Techniques; D004364:Pharmaceutical Preparations / Q000378:metabolism; D015203:Reproducibility of Results; D012107:Research Design
D004364:Pharmaceutical Preparations