Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults.
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.
['Eckermann|Gabriel|G|', 'Lahu|Gezim|G|', 'Nassr|Nassr|N|', 'Bethke|Thomas D|TD|']
D000328:Adult D000631:Aminopyridines D000889:Anti-Arrhythmia Agents D001549:Benzamides D018592:Cross-Over Studies D003521:Cyclopropanes D004077:Digoxin D004347:Drug Interactions D005260:Female D064368:Healthy Volunteers D006801:Humans D008297:Male D058988:Phosphodiesterase 4 Inhibitors D055815:Young Adult
pharmacokinetics interaction Roflumilast digoxin P-glycoprotein