title: The targeted oral, once-daily phosphodiesterase 4 inhibitor roflumilast and the leukotriene receptor antagonist montelukast do not exhibit significant pharmacokinetic interactions.
abstract: This nonrandomized, fixed-sequence, 3-period study investigated potential pharmacokinetic interactions between the leukotriene receptor antagonist montelukast, approved for the treatment of asthma, and roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor in clinical development for asthma and chronic obstructive pulmonary disease. Pharmacokinetic interactions are of interest because both drugs may be coadministered and share a common metabolic pathway via cytochrome P450 3A. Single-dose montelukast (10 mg, po) was administered alone in period 1, followed by repeated once-daily roflumilast alone (500 microg, po) for 12 days (period 2). In period 3, 500 microg qd roflumilast was coadministered with 10 mg qd montelukast for 8 days. Different pharmacokinetic parameters were evaluated for montelukast alone, for steady-state roflumilast and its pharmacologically active metabolite roflumilast N-oxide alone, for single-dose montelukast when coadministered with steady-state roflumilast, and for steady-state roflumilast and its N-oxide metabolite when coadministered with steady-state montelukast. The AUC and Cmax of montelukast were modestly increased by 9% and 8%, respectively, when single-dose montelukast was coadministered with steady-state roflumilast. The pharmacokinetics of roflumilast and roflumilast N-oxide in steady state remained unchanged when repeat-dose montelukast was coadministered at steady-state. Concomitant administration of both drugs was well tolerated. These findings suggest that no dose adjustment is warranted for either drug when roflumilast and montelukast are coadministered.
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Tübingen, Otfried-Müller-Str 45, D-72076 Tübingen, Germany. gabriele.boehmer@med.uni-tuebingen.de
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: Böhmer
authors.forename: Nassr
authors.initials: N
authors.lastname: Nassr
authors.forename: Marcus
authors.initials: M
authors.lastname: Wenger
authors.forename: Andreas
authors.initials: A
authors.lastname: Hünnemeyer
authors.forename: Gezim
authors.initials: G
authors.lastname: Lahu
authors.forename: Silke
authors.initials: S
authors.lastname: Templin
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Gleiter
authors.forename: Robert
authors.initials: R
authors.lastname: Hermann