Abstract

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.

Author Details

Authors

• T.D. Bethke¹
• M. Hartmann¹
• A. Hünnemeyer¹
• G. Lahu¹
• C.H. Gleiter²

Departments

• ¹ Nycomed GmbH, Konstanz, and
• ² Department of Clinical Pharmacology, University of Tübingen, Tübingen, Germany

Address

Dr. T.D. Bethke
Nycomed Deutschland GmbH
Moltkestrasse 4
78467 Konstanz, Germany
Email: [email protected]

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