title: Effect of clarithromycin on steady-state digoxin concentrations.
abstract: OBJECTIVE
  To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors.
  
  
  METHODS
  Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin.
  
  
  RESULTS
  Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 +/- 0.329 ng/mL; after, 1.36 +/- 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration.
  
  
  CONCLUSIONS
  Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.
authors.affiliation: Department of Pharmacy, National Cardiovascular Center, Osaka, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kodama
authors.forename: Kohji
authors.initials: K
authors.lastname: Yoneda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D004077:Digoxin; D017291:Clarithromycin