An assessment of population-based and Bayesian methods to individualize digoxin doses shortly after the start of therapy for atrial fibrillation.
The accuracy of population-based methods and of Bayesian analysis to predict individual digoxin pharmacokinetic variables have been evaluated by their ability to predict a measured peak and trough serum digoxin concentration. We studied 13 digitalized patients (three women) whose mean (range) age and weight was 65.8 (60-78) years and 76.6 (68-101.6) kg and who had stable renal function. The population-based methods (using a clearance of 48.87 + 0.87 x creatinine clearance in ml/h/kg and volume of distribution, in litres, of either 7.3 x weight (kg) or 269 + 3.12 x creatinine clearance) were more than adequate for clinical purposes. The mean prediction errors of a measured steady-state peak concentration from these two population methods were -0.074 and 0.013 microgram/l respectively, whilst those of a measured trough concentration were -0.058 and 0.005 microgram/l. Bayesian analysis, using a sample drawn 11 h after the dose on day five of therapy, gave overall the least biased and most precise of the revised estimates. The mean prediction errors of peak and trough values using this sample were 0.069 and -0.005 microgram/l respectively. As expected, the closer the sample was drawn to the time of the trough concentration the more precise were the Bayesian-derived predictions. The value of the Bayesian technique to individualize digoxin doses could not be validated because it was not possible to distinguish between this and the population methods.(ABSTRACT TRUNCATED AT 250 WORDS)
Chrystyn
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H
Postgraduate School of Studies in Pharmaceutical Technology, University of Bradford, U.K.
Dean
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S
D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D001499:Bayes Theorem; D003404:Creatinine / Q000097:blood; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D004077:Digoxin; D003404:Creatinine