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Population pharmacokinetic investigation of digoxin in Japanese infants and young children.
MedLine Citation:
PMID:  20592416     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
To establish the role of patient characteristics in estimating doses of digoxin for infants and young children using routine therapeutic drug monitoring data, the steady-state blood-level data (n = 245) after repetitive oral administration in 117 hospitalized infants and young children were analyzed using nonlinear mixed effects modeling (NONMEM), a computer program designed for analyzing drug pharmacokinetics in study populations through pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a 1-compartment pharmacokinetic model. Estimates generated by NONMEM indicated that the clearance of digoxin (CL/F; L/h) was influenced by the following demographic variables: total body weight (TBW), presence of congestive heart failure (CHF), and infant-young children clearance factor (trough serum concentration of digoxin; Conc). These influences could be modeled by the equation CL/F (L/h) = 0.302 · TBW (kg)(1.17) · 0.905(CHF) · Conc (trough serum digoxin concentration >1.7 ng/mL)(-0.540); F = 0.754, where CHF is 1 for presence of congestive heart failure, 0 otherwise; F is bioavailability, 1 for elixirs, 0.754 for powders; and Conc(-0.540) is 1 for digoxin concentration <1.7 ng/mL. Clinical application of the model to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve the desired therapeutic effect. However, the digoxin dosage regimen for the individual patient should be based on a careful appraisal of his or her clinical need for the drug.
Authors:
Miho Yukawa; Eiji Yukawa; Fumihiro Suematsu; Takako Takiguchi; Hirohito Ikeda; Hatsumi Aki; Masao Mimemoto
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Publication Detail:
Type:  Journal Article     Date:  2010-06-30
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  51     ISSN:  1552-4604     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  857-63     Citation Subset:  IM    
Affiliation:
Laboratory of Evidence-Based Pharmacotherapy, Daiichi University of Pharmacy, 22-1 Tamagawa-Cho, Minami-Ku, Fukuoka 815-8511, Japan; e-mail: yukawa@daiichi-cps.ac.jp.
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