Absence of Pharmacokinetic Interaction Between Roflumilast and Digoxin in Healthy Adults

• Published in: Journal of clinical pharmacology 2012-02, Vol.52 (2), p.251-257
• Main Authors: Eckermann, Gabriel, Lahu, Gezim, Nassr, Nassr, Bethke, Thomas D.
• Format: Article
• Language: English
• Subjects: Adult; Aminopyridines - administration & dosage; Aminopyridines - adverse effects; Aminopyridines - blood; Aminopyridines - pharmacokinetics; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - adverse effects; Anti-Arrhythmia Agents - blood; Anti-Arrhythmia Agents - pharmacokinetics; Benzamides - administration & dosage; Benzamides - adverse effects; Benzamides - blood; Benzamides - pharmacokinetics; Cross-Over Studies; Cyclopropanes - administration & dosage; Cyclopropanes - adverse effects; Cyclopropanes - blood; Cyclopropanes - pharmacokinetics; digoxin; Digoxin - administration & dosage; Digoxin - adverse effects; Digoxin - blood; Digoxin - pharmacokinetics; Drug Interactions; Female; Healthy Volunteers; Humans; interaction; Male; P-glycoprotein; pharmacokinetics; Phosphodiesterase 4 Inhibitors - administration & dosage; Phosphodiesterase 4 Inhibitors - adverse effects; Phosphodiesterase 4 Inhibitors - blood; Phosphodiesterase 4 Inhibitors - pharmacokinetics; Roflumilast; Young Adult
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270010389467

Numerous interactions are known for digoxin, which is a drug with a narrow therapeutic index and a substrate of P-glycoprotein (P-gp). This study investigated potential effects of coadministration on pharmacokinetics and safety of both drugs when a single dose of digoxin was concomitantly administered with roflumilast under steady-state conditions. Sixteen healthy male and female adults were randomly assigned in an open-label, crossover study to either of 2 treatment sequences that consisted of 2 treatment periods separated by a washout phase. Treatments were oral daily doses of roflumilast for 14 days given concomitantly on days 1 and 14 with a single oral dose of digoxin or an oral dose of digoxin once on day 1. Plasma samples for pharmacokinetic evaluations of digoxin and roflumilast concentrations with and without concomitant treatment were taken. The rate of digoxin absorption was slightly (15%) but statistically insignificantly increased, whereas the extent of absorption was not altered by concomitant medication with roflumilast. Concomitant medication with digoxin did not significantly affect steady-state pharmacokinetics of either roflumilast or its active metabolite roflumilast N-oxide. Roflumilast is not an inhibitor of P-gp. No safety or tolerability concerns were detected with coadministration of roflumilast and digoxin.