Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK.
Expert Rev Clin Pharmacol. 2011 Mar;4(2):261-74. doi: 10.1586/ecp.10.143.
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.
目前，美国食品药品监督管理局（FDA）发布的指导意见已经更新，以评估药物研发过程中肾功能损害对药物药代动力学的影响，纳入了对非肾脏消除途径药物的评估。肾功能损害不仅会影响肾脏对药物的消除，还会影响在肝脏中广泛代谢的药物的非肾脏途径。肾衰竭可能通过诱导或抑制肝酶，或通过其对其他变量（如蛋白结合、肝血流量和代谢物积累）的影响来影响肝药物代谢。对肾功能损害个体潜在暴露的模拟有助于选择安全有效的剂量方案。本文讨论了应用系统生物学方法模拟肾功能损害患者的药物处置。
