Population pharmacokinetic investigation of digoxin in Japanese neonates.

Objective: To establish the role of patient characteristics in estimating doses of digoxin for neonates using routine therapeutic drug monitoring data. Method: The steady-state blood level data (n = 129) after repetitive oral administration in 71 hospitalized neonates were analysed using Nonlinear M...

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Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 32; no. 4; pp. 381 - 387
Autores principales: Yukawa E, Akiyama K, Suematsu F, Yukawa M, Minemoto M
Formato: research Journal Article
Publicado: Wiley-Blackwell Aug2007
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2007
      vid: 32
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1111/j.1365-2710.2007.00833.x
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        atl: Population pharmacokinetic investigation of digoxin in Japanese neonates.
      aug:
        au:
          Yukawa E
          Akiyama K
          Suematsu F
          Yukawa M
          Minemoto M
        affil: Laboratory of Evidence-based Pharmacotherapy, College of Pharmaceutical Sciences, Daiichi University, Minami-Ku, Fukuoka, Japan.
      sug:
        subj:
          Cardiotonic Agents Pharmacokinetics
          Digoxin Pharmacokinetics
          Drug Monitoring
          Models, Biological
          Body Weight
          Cardiotonic Agents Administration and Dosage
          Chaos Theory
          Digoxin Administration and Dosage
          Dose-Response Relationship, Drug
          Female
          Gestational Age
          Infant, Newborn
          Japan
          Male
          Retrospective Design
          Software
          Human
          Infant, Newborn: birth-1 month
          Female
          Male
      ab: Objective: To establish the role of patient characteristics in estimating doses of digoxin for neonates using routine therapeutic drug monitoring data. Method: The steady-state blood level data (n = 129) after repetitive oral administration in 71 hospitalized neonates were analysed using Nonlinear Mixed Effects Modelling (nonmem), a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a one-compartment open pharmacokinetic model. The effect of a variety of developmental and demographic factors on digoxin disposition was investigated. Results: Estimates generated by nonmem indicated that the clearance of digoxin (CL/F; L/h) was influenced by the demographic variables: total body weight (TBW), gestational age (GA) and neonate clearance factor (trough serum concentration of digoxin; Conc). These influences could be modelled by the equation CL/F = 0.0261 x TBW (kg)(0.645) x Conc (ng/mL)(-0.724) x GA (weeks)(0.8). The interindividual variability in digoxin clearance was modelled with proportional errors. The estimated coefficient of variation was 7.0%, and the residual variability was 13.1%. Conclusion: 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 their clinical need for the drug.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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