Pharmacokinetic evaluation of roflumilast

Expert Opin Drug Metab Toxicol. 2011 Dec;7(12):1577-91. doi: 10.1517/17425255.2011.632409. Epub 2011 Nov 8.

Abstract

Introduction: Roflumilast is a selective PDE4 inhibitor recently approved for oral, once-daily treatment of severe chronic obstructive pulmonary disease (COPD). Clinical trials have demonstrated the effect of roflumilast on reducing exacerbation frequency and improving lung function in COPD, while its mode of action may offer the potential to target the inflammatory processes underlying COPD. Roflumilast is, therefore, an important addition to current therapeutic options. It is catalyzed by cytochrome P450 (CYP) 1A2 and 3A4 to its active metabolite, roflumilast N-oxide, which accounts for > 90% of roflumilast total PDE4 inhibitory activity.

Areas covered: This article reviews the pharmacokinetics of roflumilast and considers the effects of co-administration with CYP inhibitors or inducers, and other medications commonly used in patients with COPD, on the pharmacokinetics of roflumilast and roflumilast N-oxide.

Expert opinion: Roflumilast has novel anti-inflammatory activity in COPD that provides the physician with a treatment option beyond bronchodilation. It can be co-administered with many medications commonly used by patients with COPD and its anti-inflammatory activity provides incremental benefits on top of existing therapies. Future research will further elucidate the impact of roflumilast on COPD and beyond, while alternative dosing regimens may offer a means to ameliorate transient tolerability issues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aminopyridines / pharmacokinetics*
  • Aminopyridines / pharmacology*
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Benzamides / pharmacokinetics*
  • Benzamides / pharmacology*
  • Clinical Trials as Topic
  • Cyclopropanes / pharmacokinetics
  • Cyclopropanes / pharmacology
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Interactions
  • Humans
  • Phosphodiesterase 4 Inhibitors / pharmacokinetics*
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology

Substances

  • Aminopyridines
  • Anti-Inflammatory Agents
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • roflumilast N-oxide