title: [Appropriate pharmacotherapy in patients with chronic kidney disease - new approach - ].
abstract: The kidney is the most important organ for the excretion of drugs. It was previously thought that appropriate dosages of these drugs could be easily estimated by evaluating the kidney function of patients and the excretion rate of the drug. However, the pharmacokinetic characteristics of patients with kidney disease are as follows: 1) Active metabolites with a higher polarity can accumulate, which can induce unpredictable adverse effects. For example, over sedation with morphine or the development of the fatal toxic syndrome in the case of allopulinol are due to the accumulation of active metabolites derived from these drugs. 2) Although the renal excretion rate of acetoaminophen is only less than 5%, the accumulation of its glucuronide conjugate during multiple dosing in patients with kidney failure may induce high serum acetoaminophen trough levels via the entero-hepatic circulation. 3) Although the renal excretion rate of the drugs are negligible, a remarkable increase in the serum levels of certain drugs were observed in patients with end stage kidney disease, suggesting a significant reduction in non-renal clearance probably by the accumulation of uremic toxins. For drugs that are likely to be administered to patients with kidney disease, even including drugs that are not excreted by the kidney, a full pharmacokinetic study should be conducted in patients and the results carefully assessed. Information on dosing adjustments for impaired kidney function based on estimated glomerular filtration rates should then be clearly stated in the package insert of the drugs.
authors.affiliation: Division of Clinical Pharmacology, Center for Clinical Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. hirata@kumamoto-u.ac.jp
authors.forename: Sumio
authors.initials: S
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004334:Drug Administration Schedule; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D051381:Rats; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism; D014511:Uremia / Q000201:enzymology
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System