title: Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients.
abstract: BACKGROUND
  hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have important clinical implications with respect to the risk of developing aminoglycoside-associated nephrotoxicity in patients treated with once daily dosing regimens.
  
  
  OBJECTIVE
  To examine the effect of the time period of administration on aminoglycoside exposure and the incidence of nephrotoxicity in a large population of hospitalized patients with serious infections.
  
  
  METHODS
  General ward and intensive care unit of a teaching hospital.
  
  
  METHODS
  In this retrospective cohort study, patients treated with intravenous tobramycin or gentamicin were eligible for inclusion. Patients were divided into three groups by time of administration: morning, afternoon and night.
  
  
  METHODS
  Pharmacokinetic parameters and the incidences of nephrotoxicity were compared between the morning, afternoon and evening groups. Results 310 general ward and 411 intensive care unit patients were included. No significant differences were found in patient characteristics between the morning, afternoon and night groups. The time period of administration did not affect aminoglycoside pharmacokinetics or the incidence of nephrotoxicity.
  
  
  CONCLUSIONS
  The time of administration has no effect on the pharmacokinetics or nephrotoxicity of once daily dosed aminoglycosides in hospitalized patients. Consequently, we advise aminoglycosides to be administered as soon as possible in case of (suspected) severe hospital-acquired infections and subsequent dosages to be based on therapeutic drug monitoring to optimize the efficacy/toxicity balance.
authors.affiliation: Department of Clinical Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands, E.M.vanmaarseveen@UMCUtrecht.nl.
authors.forename: Erik
authors.initials: E
authors.lastname: van Maarseveen
authors.forename: Wai Hong
authors.initials: WH
authors.lastname: Man
authors.forename: Johannes
authors.initials: J
authors.lastname: Proost
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.forename: Daniël
authors.initials: D
authors.lastname: Touw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000067573:Chronopharmacokinetics; D015331:Cohort Studies; D003141:Communicable Diseases / Q000188:drug therapy* / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization / Q000639:trends; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000617:Aminoglycosides