Current guidance issued by the US FDA to assess the impact of renal impairment on the pharmacokinetics of a drug under development has recently been updated to include evaluation of drugs with non-renal elimination routes. Renal impairment not only affects elimination of the drug in the kidney, but also the non-renal route of drugs that are extensively metabolized in the liver. Renal failure may influence hepatic drug metabolism either by inducing or suppressing hepatic enzymes, or by its effects on other variables such as protein binding, hepatic blood flow and accumulation of metabolites. Prior simulation of the potential exposure of individuals with renal impairment may help in the selection of a safe and effective dosage regimen. In this article, we discuss the application of a systems biology approach to simulate drug disposition in subjects with renal impairment.
March 1, 2011
Author(s): Karen Rowland Yeo, Mohsen Aarabi, Masoud Jamei, Amin Rostami-Hodjegan
Year: March 1, 2011