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Abstract
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 nonrenal elimination routes. Renal impairment not only affects elimination of the drug in the kidney, but also the nonrenal 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.
Acknowledgement
The authors thank James Kay for his assistance with the preparation of this manuscript.
Financial & competing interests disclosure
This work was funded by Simcyp Limited and the authors are employees of, and/or shareholders in, the company. Simcyp Simulator is freely available, following completion of the training workshop, to approved members of academic institutions and other nonprofit organizations for research and teaching purposes. Mohsen Aarabi has no conflicts of interest that are directly relevant to the contents of this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.