title: Diagnostic accuracy of a hyperbolic model in predicting digoxin concentrations based on glomerular filtration rates.
abstract: BACKGROUND
  Inappropriate doses and high serum concentrations of digoxin are highly prevalent in patients with renal impairment, and the drug dosage adjustment according to the glomerular filtration rate (GFR) is recommended. The aim of our study was to evaluate the dependence degree of digoxin total clearance (CL) on GFR, and the diagnostic efficiency of a predictive model for serum digoxin steady-state concentrations (Css) from estimated GFR by Cockcroft-Gault formula.
  
  
  METHODS
  In 400 outpatients treated orally with digoxin, serum Css were determined (fluorescence polarization immunoassay from Abbott Laboratories), and total CL was calculated. The prediction of Css was carried out using a hyperbolic model developed by Konishi et al in Japan (J Clin Pharm Ther 2002;27:257), and the constants of the equation were modified for a Caucasian population.
  
  
  RESULTS
  Only 26% of the digoxin CL interindividual variability may be explained by differences in GFR, and this fact is a serious limitation for the derived predictive models. A 65% diagnostic efficiency was obtained for original and modified hyperbolic models in the correct classification of predicted Css as subtherapeutic, therapeutic or supratherapeutic with respect to obtained Css concentrations.
  
  
  CONCLUSIONS
  The diagnostic efficiency obtained in the prediction of serum digoxin concentrations from estimated GFR values is unacceptable for the drug dosage adjustment in clinical practice.
authors.affiliation: Pharmacy Department, University Clinical Hospital, Health Research Institute, IDIS, Santiago de Compostela, A Coruña, Spain. josecarlostutor@redfarma.org
authors.forename: J
authors.initials: J
authors.lastname: González-López
authors.forename: J C
authors.initials: JC
authors.lastname: Tutor
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009994:Osmolar Concentration; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044465:White People; D055815:Young Adult
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin