title: Population pharmacokinetics and optimization of the dosing regimen of digoxin in adult patients.
abstract: BACKGROUND
  This study aimed to evaluate the population pharmacokinetics of digoxin in Japanese patients and establish a dosage regimen based on the pharmacokinetic data.
  
  
  METHODS
  We analyzed 287 serum digoxin samples from 192 individuals by using the nonlinear mixed effects model. We used simulations to optimize the dosage regimen of digoxin to achieve a high likelihood of the target concentration (0.5-0.8 ng/mL).
  
  
  RESULTS
  The total body clearance (CL/F ([L/h]) was calculated using the following formula: CL/F = (1.21 + 0.0532 × CLcr [(mL/min]) × (1 + 0.787 × AMD), where CLcr is the creatinine clearance and AMD is 0 in the case of concomitant administration of amiodarone and 1 otherwise. To achieve the target concentration (0.5-0.8 ng/mL), the dosage of digoxin was 0.0625 mg/day (CLcr < 35 mL/min and AMD = 0); 0.125 mg/day (CLcr, 35-65 mL/min and AMD = 0); 0.1875 mg/day (CLcr, 65-100 mL/min and AMD = 0); 0.0625 mg/every other day (CLcr < 30 mL/min and AMD = 1); and 0.0625 mg/day (CLcr, 30-85 mL/min and AMD = 1).
  
  
  CONCLUSIONS
  Our findings suggest that population parameters are useful for evaluating digoxin pharmacokinetics.
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Futaba
authors.initials: F
authors.lastname: Miyaji
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inomata
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ako
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Atsuda
keywords: Digoxin; Dosage regimen; Population pharmacokinetics
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