title: Toxicogenetics in drug development.
abstract: The major progress made in the understanding of the genetic basis of inter-individual variation in drug response, alongside the rapid advances in technology, provides major new opportunities to ensure the safe introduction of a new chemical entity into clinical practice. In essence, the aim is to get the right drug into the right patient using knowledge of factors that influence both benefit and risk. The stage of the drug development process at which genetic analysis needs to be undertaken is dependent on the frequency of the event, and the availability of clinical samples. Thus, common adverse events, or assessment of efficacy, will be feasible for testing in phases I-III. However, when a rare event is being studied, for example idiosyncratic toxicity, prospective analysis becomes impossible. Thus, retrospective studies using available drugs is important as it may provide paradigms for future drug development. Additionally, prospective collection of samples will be important so that rare adverse events identified during phase IV can then be analysed using toxicogenetic approaches. Ultimately, information obtained from toxicogenetics must be included in the Specific Product Characteristics (SPC) and thus formally translated into clinical practice in order to contraindicate the drug in specific patients with a genetically determined susceptibility to drug toxicity.
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Liverpool, P.O. Box 147, Ashton Street, L69 3GE, Liverpool, UK. bkpark@liv.ac.uk
authors.forename: B K
authors.initials: BK
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D002220:Carbamazepine / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004342:Drug Hypersensitivity / Q000209:etiology; D004345:Drug Industry; D014644:Genetic Variation; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013449:Sulfonamides / Q000009:adverse effects; D014116:Toxicology
chemical_list: D013449:Sulfonamides; D002220:Carbamazepine