ArticleBritish journal of clinical pharmacology2009
Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects.
Article in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 48 citations in OpenAlex.
- Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib in patients with multiple myeloma or non-Hodgkin's lymphoma.Clinical pharmacokinetics · 2011Trial
- No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study.BMC clinical pharmacology · 2011Trial
- Pharmacokinetic drug interactions with vandetanib during coadministration with rifampicin or itraconazole.Drugs in R&D · 2011Trial
- Polypharmacy and Drug-Drug Interactions in Chronic Obstructive Pulmonary Disease: A Narrative Clinical Review.Pharmaceutics · 2026Review
- Investigating the therapeutic potential of polymeric roflumilast nanosuspension in modulating asthma hallmarks using an in vivo ovalbumin model.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.Research square · 2026Article
- High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach.Frontiers in pharmacology · 2025Article
- Insights into Inhalation Drug Disposition: The Roles of Pulmonary Drug-Metabolizing Enzymes and Transporters.International journal of molecular sciences · 2024Review
- Prediction of drug-drug interactions between roflumilast and CYP3A4/1A2 perpetrators using a physiologically-based pharmacokinetic (PBPK) approach.BMC pharmacology & toxicology · 2024Article
- Clinical assessment of gepotidacin (GSK2140944) as a victim and perpetrator of drug-drug interactions via CYP3A metabolism and transporters.Clinical and translational science · 2023Article
- Virtual Screening of DrugBank Reveals Two Drugs as New BCRP Inhibitors.SLAS discovery : advancing life sciences R & D · 2017Article
- Roflumilast (daliresp): a novel phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease.P & T : a peer-reviewed journal for formulary management · 2012Article
- Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease.British journal of pharmacology · 2011Review
- Roflumilast, a Novel Phosphodiesterase 4 Inhibitor, for COPD Patients with a History of Exacerbations.Clinical medicine insights. Circulatory, respiratory and pulmonary medicine · 2011Article
- Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model.Clinical pharmacokinetics · 2010Article
- Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD.Drug design, development and therapy · 2010Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo evaluate the effect of co-administration of rifampicin, an inducer of cytochrome P450 (CYP)3A4, on the pharmacokinetics of roflumilast and roflumilast N-oxide. Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor, being developed for the treatment of chronic obstructive pulmonary disease. Roflumilast is metabolized by CYP3A4 and CYP1A2, with further involvement of CYP2C19 and extrahepatic CYP1A1. In vivo, roflumilast N-oxide contributes >90% to the total PDE4 inhibitory activity.
methodsSixteen healthy male subjects were enrolled in an open-label, three-period, fixed-sequence study. They received a single oral dose of roflumilast 500 microg on days 1 and 12 and repeated oral doses of rifampicin 600 mg once daily on days 5-15. Plasma concentrations of roflumilast and roflumilast N-oxide were measured for up to 96 h. Test/Reference ratios and 90% confidence intervals (CIs) of geometric means for AUC and C(max) of roflumilast and roflumilast N-oxide and for oral apparent clearance (CL/F) of roflumilast were estimated.
resultsDuring the steady-state of rifampicin, the AUC(0-infinity) of roflumilast decreased by 80% (point estimate 0.21; 90% CI 0.16, 0.27); C(max) by 68% (0.32; CI 0.26, 0.39); for roflumilast N-oxide, the AUC(0-infinity) decreased by 56% (0.44; CI 0.36, 0.55); C(max) increased by 30% (1.30; 1.15, 1.48); total PDE4 inhibitory activity decreased by 58% (0.42; 0.38, 0.48).
conclusionsCo-administration of rifampicin and roflumilast led to a reduction in total PDE4 inhibitory activity of roflumilast by about 58%. The use of potent cytochrome P450 inducers may reduce the therapeutic effect of roflumilast.
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