3‐Hydroxy‐3‐methylglutaryl–coenzyme a Reductase Inhibitors (statins) and Genetic Variability (Single Nucleotide Polymorphisms) in a Hepatic Drug Uptake Transporter: What's it all About?

t o t c g S t o O a Historically, metabolism had been viewed as a major eterminant of drug disposition. In recent years, howver, clear evidence has emerged to suggest that memrane transporters are also critically important. Indeed, he role of efflux transporters such as the product of the DR1 gene, P-glycoprotein, in disposition and drug ffect has been clearly established and widely studied. oreover, single nucleotide polymorphisms (SNPs) in DR1 have also been a focus of numerous studies and ay play a role in the disposition of many drugs in linical use, including human immunodeficiency virus rotease inhibitors, digoxin, fexofenadine, and cycloporine (INN, ciclosporin). However, the directional ovement of drugs across organs such as the gastroinestinal tract, liver, and kidney requires the presence nd coordinate activity of drug uptake, as well as efflux ransporters. For example, uptake transporters exressed on the basolateral domain of hepatocytes faciltate the cellular accumulation of drug substrates, beore metabolism and efflux by transporter-mediated xcretion into bile (Fig 1). Among the uptake transporters, members of the oranic anion transporting polypeptides (OATPs) have