The targeted oral, once-daily phosphodiesterase 4 inhibitor roflumilast and the leukotriene receptor antagonist montelukast do not exhibit significant pharmacokinetic interactions.
J Clin Pharmacol
; 49(4): 389-97, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19318692
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.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
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Quinolinas
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Benzamidas
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Antiasmáticos
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Antagonistas de Leucotrienos
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Aminopiridinas
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Acetatos
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article