Pharmacogenetics and pharmacovigilance.

Many different types of drugs are available to treat a wide variety of disorders. Why some patients respond to a particular drug and others do not respond, or why some patients tolerate a drug well and others are intolerant of the same drug, are obviously important clinical issues in medicine. Genetic differences among patients may contribute to differences in medication response, as well as the development of adverse effects. ‘Pharmacogenomics’ and ‘pharmacogenetics’ are terms that refer to the use of molecular genetic approaches to understand differences in drug response and tolerability. Although the two terms are sometimes used interchangeably, pharmacogenetics is, more specifically, the study of specific single nucleotide polymorphisms (SNPs) at specific genes with known functions that could plausibly be linked to drug response, whereas pharmacogenomics refers to whole genome scanning to find SNPs that might be associated with a drug response, but without necessarily knowing the function of the identified SNPs. One approach to understanding pharmacogenetic differences in drug response and tolerability is through the study of pharmacokinetics. In this issue of Drug Safety, van Puijenbroek and colleagues describe the results of a study whose objective was to investigate the feasibility of a method for informing physicians or pharmacists who report adverse drug reactions (ADRs) about the possible involvement of a genetic polymorphism in the ADR and to recommend subsequent genotyping of patients based on this possibility. The method involved the review of spontaneous ADR reports received by the Netherlands Pharmacovigilance Centre (NPC). Trained assessors at the NPC (a physician or pharmacist) evaluated each ADR report. For this study, reports were included if there was a strong suspicion by the NPC assessor of involvement of a possible genetic polymorphism of the cytochrome P450 (CYP) 2D6, 2C19 or 2C9 hepatic metabolic enzymes relevant to the drug in question. After identification of an eligible case, a feedback letter was sent by the NPC to the ADR reporter describing the study and the recommendation for genotyping. Whether genotyping was conducted was at the discretion of the patient’s treating physician. Based on their findings, van Puijenbroek and colleagues concluded that the strength of a pharmacovigilance centre is that it can combine information from different sources in the assessment of the causal relationship between intake of drugs and ADRs, and, based on this information, that it can initiate genotyping of patients for polymorphisms in drug metabolizing enzymes (DMEs). Although the concept of incorporating pharmacogenetic information into a pharmacovigilance system makes sense in theory and has potentially important personal and public health implications, the clinical utility of a system is only as good as the individual components. The system described in this paper illustrates many of the real and potential problems in applying pharmacogenetic technology to pharmacovigilance and patient care. The interpretation of ADR reports is important for pharmacovigilance and pharmacogenetic studies. Establishing causality between drug use and a ‘reaction’ is a difficult and complex process. For a patient taking a drug or COMMENTARY Drug Safety 2009; 32 (3): 265-270 0114-5916/09/0003-0265/$49.95/0