Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide
| Autor: | Martin Elmlinger, Markus Hinder, Gezim Lahu, Nassr Nassr, Peter Ruth, Andreas Huennemeyer, Rolf Herzog |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Cyclopropanes Enoxacin Male Cytochrome P-450 CYP1A2 Inhibitors Administration Oral Aminopyridines Pharmacology Young Adult Pharmacokinetics medicine Cytochrome P-450 CYP3A Humans Pharmacology (medical) Clinical significance Drug Interactions Roflumilast COPD CYP3A4 business.industry CYP1A2 medicine.disease Tolerability Benzamides Female Phosphodiesterase 4 Inhibitors business medicine.drug |
| Zdroj: | Journal of clinical pharmacology. 51(4) |
| ISSN: | 1552-4604 |
| Popis: | Roflumilast is an oral phosphodiesterase 4 (PDE4) inhibitor for the treatment of chronic obstructive pulmonary disease (COPD). It is metabolized by CYP1A2 and CYP3A4 to its primary metabolite, roflumilast N-oxide, through which >90% total PDE4 inhibitory activity (tPDE4i) is mediated. Fluoroquinolones, of which enoxacin is the most potent CYP1A2 inhibitor, are used to treat COPD exacerbations. This phase I, open, nonrandomized, fixed-sequence, 2-period study evaluated the effects of steady-state enoxacin on the single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. Twenty healthy participants received roflumilast, 500 μg once daily, on days 1 and 12, and enoxacin, 400 mg twice daily, on days 7 to 18. Pharmacokinetic profiles were obtained for days 1 to 6 and 12 to 1 9. The safety and tolerability of all treatments were also assessed. In 1 9 evaluable participants, coadministration led to 56% higher mean systemic exposure, 20% higher mean peak concentrations, and 36% lower mean apparent oral clearance compared with roflumilast alone. For roflumilast N-oxide, 23% higher mean systemic exposure and 14% lower mean peak concentrations were seen after coadministration. Roflumilast was well tolerated both alone and in combination with enoxacin. A weak interaction was shown between roflumilast and enoxacin, as mean tPDE4i increased by 25%, but is unlikely to have clinical relevance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text