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The Effect of Erythromycin and Clarithromycin on the Pharmacokinetics of Intravenous Digoxin in Healthy Volunteers
Author(s) -
Tsutsumi Kimiko,
Kotegawa Tsutomu,
Kuranari Masae,
Otani Yasukiyo,
Morimoto Takuya,
Matsuki Shunji,
Nakano Shigeyuki
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127002237992
Subject(s) - digoxin , clarithromycin , erythromycin , pharmacokinetics , pharmacology , drug interaction , medicine , oral administration , antibiotics , chemistry , heart failure , biochemistry , helicobacter pylori
Several case reports have suggested an interaction between digoxin and macrolide antibiotics. The authors investigated the effect of erythromycin and clarithromycin on the pharmacokinetics of intravenously administered digoxin (0.5 mg) in healthy subjects. Nine male subjects participated in three studies (digoxin alone, digoxin with erythromycin, and digoxin with clarithromycin). Subjects took erythromycin (800 mg per day) or clarithromycin (400 mg per day) on the day before digoxin dosing and during the kinetic study. Neither of the macrolides affected serum digoxin concentration‐time curves. However, more than 1.3‐fold increases in urinary digoxin excretions were observed during erythromycin and clarithromycin coadministration compared with digoxin alone. There were significant differences in renal clearance between macrolide coadministration and the control condition (digoxin alone: 98.4 ml/min; digoxin with erythromycin: 137.3 ml/min; digoxin with clarithromycin: 133.6ml/min). In conclusion, neither erythromycin nor clarithromycin has a significant effect on serum digoxin disposition after an intravenous administration. Renal digoxin excretion is not inhibited but rather enhanced by both macrolides.