title: A population pharmacokinetic analysis of the influence of nutritional status of digoxin in hospitalized Korean patients.
abstract: BACKGROUND
  Safe and effective use of digoxin in hospitalized populations requires information about the drug's pharmacokinetics and the influence of various factors on drug disposition. However, no attempts have been made to link an individual's digoxin requirements with nutritional status.
  
  
  OBJECTIVE
  The main goal of this study was to estimate the population pharmacokinetics of digoxin and to identify the nutritional status that explains pharmacokinetic variability in hospitalized Korean patients.
  
  
  METHODS
  Routine therapeutic drug-monitoring data from 106 patients who received oral digoxin at Seoul National University Bundang Hospital were retrospectively collected. The pharmacokinetics of digoxin were analyzed with a 1-compartment, open-label pharmacokinetic model by using a nonlinear mixed-effects modeling tool (NONMEM) and a multiple trough screening approach.
  
  
  RESULTS
  The effect of demographic characteristics and biochemical and nutritional indices were explored. Estimates generated by using NONMEM indicated that the CL/F of digoxin was influenced by renal function, serum potassium, age, and percentage of ideal body weight (PIBW). These influences could be modeled by following the equation CL/F (L/h) = 1.36 × (creatinine clearance/50)(1.580) × K(0.835) × 0.055 × (age/65) × (PIBW/100)(0.403). The interindividual %CV for CL/F was 34.3%, and the residual variability (SD) between observed and predicted concentrations was 0.225 μg/L. The median estimates from a bootstrap procedure were comparable and within 5% of the estimates from NONMEM. Correlation analysis with the validation group showed a linear correlation between observed and predicted values.
  
  
  CONCLUSIONS
  The use of this model in routine therapeutic drug monitoring requires that certain conditions be met which are consistent with the conditions of the subpopulations in the present study. Therefore, further studies are needed to clarify the effects of nutritional status on digoxin pharmacokinetics. The present study established important sources of variability in digoxin pharmacokinetics and highlighted the relationship between pharmacokinetic parameters and nutritional status in hospitalized Korean patients.
authors.affiliation: Department of Pharmacy, Seoul National University Bundang Hospital, Seoul, South Korea.
authors.forename: Soo An
authors.initials: SA
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors.forename: Hwi-yeol
authors.initials: HY
authors.lastname: Yun
authors.affiliation: Department of Pharmacy, Seoul National University Bundang Hospital, Seoul, South Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea. Electronic address: wgshin@snu.ac.kr.
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D004077:Digoxin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D009752:Nutritional Status; D011188:Potassium / Q000097:blood; D056910:Republic of Korea; D012189:Retrospective Studies
chemical_list: D004077:Digoxin; D011188:Potassium
keywords: NONMEM; digoxin; nonlinear mixed-effects modeling; nutritional status; population pharmacokinetics