All important drug interactions, with the possible exception of idiosyncratic or allergic reactions, have a pharmacokinetic or pharmacodynamic basis, or both (1). A study of the mechanisms of drug interactions is of much value in selecting proper drug combinations in order to provide rational therapy, especially for drugs that have a narrow margin of safety and where drugs are used for a prolonged period of time. Most recently, pharmacogenetics has linked drug interaction outcomes to variations in genes encoding cytochrome P450 (CYP) enzymes (2) and transporter genes.Statins (or HMG-CoA reductase inhibitors) represent a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. As of 2010, a number of statins have been on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin (3).Statins are associated with two uncommon, but important, adverse effects, asymptomatic elevation in liver enzyme activity and myopathy. In 2001, cerivastatin was withdrawn from the market worldwide because of an unacceptably high incidence of serious The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT--P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review summarizes the most important interactions of statins.

BackgroundOver the past 25 years, there has been growing recognition of the importance of studying the Ethical, Legal and Social Implications (ELSI) of genetic and genomic research. A large investment into ELSI research from the National Institutes of Health (NIH) Human Genomic Project budget in 1990 stimulated the growth of this emerging field; ELSI research has continued to develop and is starting to emerge as a field in its own right. The evolving subject matter of ELSI research continues to raise new research questions as well as prompt re-evaluation of earlier work and a growing number of scholars working in this area now identify themselves as ELSI scholars rather than with a particular discipline.Main textDue to the international and interdisciplinary nature of ELSI research, scholars can often find themselves isolated from disciplinary or regionally situated support structures. We conducted a workshop with Early Career Researchers (ECRs) in Oxford, UK, and this paper discusses some of the particular challenges that were highlighted. While ELSI ECRs may face many of the universal challenges faced by ECRs, we argue that a number of challenges are either unique or exacerbated in the case of ELSI ECRs and discuss some of the reasons as to why this may be the case. We identify some of the most pressing issues for ELSI ECRs as: interdisciplinary angst and expertise, isolation from traditional support structures, limited resources and funding opportunities, and uncertainty regarding how research contributions will be measured. We discuss the potential opportunity to use web 2.0 technologies to transform academic support structures and address some of the challenges faced by ELSI ECRs, by helping to facilitate mentoring and support, access to resources and new accreditation metrics.ConclusionAs our field develops it is crucial for the ELSI community to continue looking forward to identify how emerging digital solutions can be used to facilitate the international and interdisciplinary research we perform, and to offer support for those embarking on, progressing through, and transitioning into an ELSI research career.

To investigate whether chronic statin treatment after coronary artery bypass grafting (CABG) protects patients from major cardiac events and provides percutaneous coronary intervention (PCI) free survival.