title: Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy.
abstract: OBJECTIVE
  Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max).
  
  
  METHODS
  We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method).
  
  
  RESULTS
  For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10-20% by the two-point method and by up to 30% with a large variation by the Bayesian method.
  
  
  CONCLUSIONS
  The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8-10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospital Basel, 4031, Basel, Switzerland.
authors.forename: Lana
authors.initials: L
authors.lastname: Nezic
authors.forename: Adrian
authors.initials: A
authors.lastname: Derungs
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruggisser
authors.forename: Sarah
authors.initials: S
authors.lastname: Tschudin-Sutter
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.forename: Manuel
authors.initials: M
authors.lastname: Haschke
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001499:Bayes Theorem; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents
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