Influence of renal impairment on the pharmacokinetics of oral roflumilast: an open-label, parallel-group, single-center study.

OBJECTIVE

Roflumilast is a novel, orally active, selective phosphodiesterase 4 inhibitor recently approved in the European Union for the treatment of severe COPD. Roflumilast and its metabolites are mainly (70% of total radioactivity) eliminated via the kidneys as glucuronides. The potential impact of renal impairment on the pharmacokinetics of roflumilast and its active main metabolite roflumilast N-oxide were characterized.

MATERIALS AND METHODS

Patients (n = 12) with severe renal impairment (creatinine clearance CL(CR) < 30 ml/ min/1.73 m²; otherwise healthy) and matched (sex, age, weight, and height) healthy control subjects (n = 12; CL(CR) > 80 ml/min/1.73 m²) were enrolled into an open-label, parallelgroup study. Single dose (500 μg, p.o.) pharmacokinetics and safety/tolerability of roflumilast and roflumilast N-oxide were compared between both groups.

RESULTS

A minor decrease of exposure (area under the plasma concentration-time curve from time zero to infinity (AUC(0-∞)), maximum plasma concentration (C(max))) and a small increase in elimination half-life (t(1/2)) of roflumilast (-1%; -6%; +19%, respectively) and roflumilast N-oxide (-%; ND; +30%, respectively) were observed in renally impaired patients compared with healthy subjects. No relevant differences in safety and tolerability were observed between groups.

CONCLUSIONS

The pharmacokinetic changes observed in patients with renal impairment are of small magnitude without clinical importance. A dose adjustment or a change in the administration interval of roflumilast is not necessary in patients with renal impairment.