Premium
The Oral, Once‐Daily Phosphodiesterase 4 Inhibitor Roflumilast Lacks Relevant Pharmacokinetic Interactions With Inhaled Budesonide
Author(s) -
Hermann Robert,
Siegmund Werner,
Giessmann Thomas,
Westphal Kristin,
Weinbrenner Anita,
Hauns Bernhard,
Reutter Felix,
Zech Karl,
Lahu Gezim,
Bethke Thomas D.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007300950
Subject(s) - roflumilast , budesonide , pharmacokinetics , tolerability , pharmacology , crossover study , bioequivalence , medicine , area under the curve , oral administration , anesthesia , inhalation , adverse effect , placebo , copd , alternative medicine , pathology
This open‐label, randomized, 3‐period crossover study evaluated the pharmacokinetic interaction potential of roflumilast and budesonide following repeated coadministration to healthy male subjects (N = 12). Treatments consisted of oral roflumilast 500 μg, once daily, orally inhaled budesonide 800 μg, twice daily, and concomitant administration of both treatments for 7 days each. Roflumilast and roflumilast N‐oxide in plasma and budesonide serum levels were measured by specific assays. Geometric mean test/reference ratios of steady‐state pharmacokinetic parameters were evaluated by analysis of variance. Safety and tolerability were monitored. Pharmacokinetic parameters of roflumilast, roflumilast N‐oxide, and budesonide after coadministration of roflumilast and budesonide were similar to those after mono‐treatment. Compared with budesonide and roflumilast mono‐treatments, slightly lower maximum serum/plasma concentration (C max ) and area under the curve (AUC) values of roflumilast N‐oxide and budesonide (ranging from −8% to −16%) were observed with combined treatment. All test/reference ratios were within predefined equivalence acceptance ranges for roflumilast AUC (0.80, 1.25) and C max (0.70, 1.43) and for roflumilast N‐oxide and budesonide AUC and C max (all 0.67, 1.50). Coadministration of roflumilast and budesonide did not alter the steady‐state disposition of each other and did not affect safety and tolerability of either drug.