Translational Medicine
Clinical Pharmacology & Therapeutics (2008); 83, 6, 898–903 doi:10.1038/clpt.2008.59
Emerging Evidence of the Impact of Kidney Disease on Drug Metabolism and Transport
TD Nolin1,2, J Naud3,4, FA Leblond3 and V Pichette3,4
- 1Division of Nephrology and Transplantation, Department of Medicine, Maine Medical Center, Portland, Maine, USA
- 2Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine, USA
- 3Service de néphrologie et Centre de recherche, Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada
- 4Département de Pharmacologie, Université de Montréal, Montréal, Québec, Canada
Correspondence: V Pichette, (vpichette.hmr@ssss.gouv.qc.ca)
Received 7 January 2008; Accepted 19 February 2008; Published online 2 April 2008.
Abstract
Several lines of emerging evidence indicate that kidney disease differentially affects uptake and efflux transporters and metabolic enzymes in the liver and gastrointestinal (GI) tract, and uremic toxins have been implicated as the cause. In patients with kidney disease, even drugs that are eliminated by nonrenal transport and metabolism could lead to important unintended consequences if they are administered without dose adjustment for reduced renal function. This is particularly so in the case of drugs with narrow therapeutic windows and may translate into clinically significant variations in exposure and response.
