Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects.
Int J Clin Pharmacol Ther
; 44(11): 572-9, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-17176624
ABSTRACT
OBJECTIVE:
Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor under investigation for the treatment of chronic obstructive pulmonary disease and asthma. In clinical practice, the drug is likely to be co-administered with inhaled bronchodilating beta2-adrenoceptor agonists. Therefore, this study investigated the pharmacokinetic characteristics of roflumilast and its pharmacodynamically active metabolite roflumilast N-oxide when co-administered with orally inhaled salbutamol in healthy subjects.METHODS:
In this open, randomized clinical study, 12 healthy male subjects received repeated doses of oral roflumilast 500 microg once daily, orally inhaled salbutamol 200 microg 3 times daily, and a combination of both drugs over 7 days according to a 3-period, changeover design with 14 days washout between treatments.RESULTS:
Co-administration of roflumilast and salbutamol did not markedly change roflumilast or roflumilast N-oxide disposition. Point estimates (90% confidence intervals) of area under the curve from 0-24 h (AUC 0-24) and maximum plasma concentration in steady state (Cmax,ss) for roflumilast with salbutamol versus roflumilast alone were 1.05 (0.94, 1.17) and 0.97 (0.84, 1.10); the respective point estimates (90% confidence intervals) for AUC 0-24 and Cmax,ss of roflumilast N-oxide were 0.98 (0.91, 1.06) and 0.98 (0.92, 1.03). Roflumilast co-administration did not alter the pharmacokinetics of steady state salbutamol. The respective point estimates (90% confidence intervals) for AUC 0-6 and Cmax,ss of salbutamol with roflumilast versus salbutamol alone were 1.10 (0.99, 1.21), 1.08 (0.91, 1.28). The combination of both drugs was well tolerated.CONCLUSION:
There were no relevant pharmacokinetic interactions between roflumilast and salbutamol at therapeutically effective doses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
Benzamidas
/
Broncodilatadores
/
Agonistas Adrenérgicos beta
/
Albuterol
/
Aminopiridinas
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Alemanha