New and simple method for estimating metildigoxin dosing regimens by multiple trough screen analysis.
The pharmacokinetics of digitalis glycosides were studied using routine therapeutic drug monitoring data to evaluate the role of patient characteristics for estimating metildigoxin dosing regimens. The 232 serum glycoside concentration data at steady-state after repetitive oral administration in 144 hospitalized patients was analyzed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. Pharmacokinetic analysis of digitalis glycosides was described using a simple steady-state pharmacokinetic model. The effect of a variety of developmental and demographic factors on glycoside clearance was investigated. NONMEM estimates indicated that this digitalis glycoside clearance was influenced by the demographic variables of age, total body weight, serum creatinine, gender, daily dose and the coadministration of spironolactone. An elderly patient was expected to have a lower rate of clearance than a young patient of equal body weight and serum creatinine. The interindividual variability in glycoside clearance was modelled with proportional error with an estimated coefficient of variation of 19.7% and the residual variability was 21.8% The dosing method based on glycoside clearance value obtained by NONMEM analysis allowed the prediction of the minimum steady-state glycoside concentration as a function of metildigoxin maintenance dose with acceptable error for therapeutic drug monitoring.
Yukawa
E
E
Division of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008297:Male; D008520:Medigoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D008520:Medigoxin