title: Pharmacokinetic considerations in chronic kidney disease and patients requiring dialysis.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is the progressive decline in renal function over time. Patients with end-stage renal disease require renal replacement therapy such as hemodialysis to support life. Hemodialysis patients require several medications to treat a variety of comorbid conditions. Polypharmacy accompanied by alterations in the pharmacokinetics of medications places hemodialysis patients at increased risk of drug accumulation and adverse events.
  
  
  METHODS
  We review alterations in the pharmacokinetics of drugs in hemodialysis patients. The major areas of pharmacokinetics, absorption, distribution, metabolism and excretion, are covered and, where appropriate, differences between dialysis patients and non-dialysis CKD patients are compared. In addition, we review the importance of drug dialyzability and its potential impact on drug efficacy. Finally, we describe important clinical examples demonstrating nonrenal drug clearance is significantly altered in CKD.
  
  
  CONCLUSIONS
  Decreases in renal drug excretion experienced by hemodialysis patients have been known for years. Recent animal and human clinical pharmacokinetic studies have highlighted that nonrenal clearance of drugs is also substantially decreased in CKD. Clinical pharmacokinetic studies are required to determine the optimal dosage of drugs in CKD and hemodialysis patients in order to decrease the incidence of adverse medication events in these patient populations.
authors: Western University, Schulich School of Medicine and Dentistry, Department of Physiology and Pharmacology , London, Ontario , Canada.
authors: Thomas J
authors: TJ
authors: Velenosi
authors: Bradley L
authors: BL
authors: Urquhart
mesh_terms: D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010599:Pharmacokinetics; D019338:Polypharmacy; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology* / Q000628:therapy
chemical_list: D004364:Pharmaceutical Preparations
keywords: dialytic clearance; drug metabolism; drug transporter; hemodialysis; pharmacokinetics