Lahu Gezim, Huennemeyer Andreas, von Richter Oliver, Hermann Robert, Herzog Rolf, McCracken Nigel, Zech Karl
Nycomed GmbH, Department of Pharmacometrics and Pharmacokinetics, Byk-Gulden-Str. 2, 78467 Konstanz, Germany.
J Clin Pharmacol. 2008 Nov;48(11):1339-49. doi: 10.1177/0091270008321941. Epub 2008 Aug 29.
Effects of single and multiple doses of oral ketoconazole on roflumilast and its active metabolite, roflumilast N-oxide, were investigated in healthy subjects. In study 1, subjects (n = 26) received oral roflumilast 500 microg once daily for 11 days and a concomitant 200-mg single dose of ketoconazole on day 11. In study 2, subjects (n = 16) received oral roflumilast 500 microg on days 1 and 11 and a repeated dose of ketoconazole 200 mg twice daily from days 8 to 20. Coadministration of single-dose ketoconazole with steady-state roflumilast increased the AUC of roflumilast by 34%; C(max) was unchanged. For roflumilast N-oxide, AUC and C(max) decreased by 12% and 20%, respectively. Repeated doses of ketoconazole increased the AUC and C(max) of roflumilast by 99% and 23%, respectively; for roflumilast N-oxide, AUC was unchanged, and C(max) decreased by 38%. No clinically relevant adverse events were observed. Coadministration of ketoconazole and roflumilast does not require dose adjustment of roflumilast.
在健康受试者中研究了单剂量和多剂量口服酮康唑对罗氟司特及其活性代谢物罗氟司特N - 氧化物的影响。在研究1中，受试者（n = 26）每天口服一次500微克罗氟司特，共11天，并在第11天同时给予200毫克单剂量酮康唑。在研究2中，受试者（n = 16）在第1天和第11天口服500微克罗氟司特，并在第8天至第20天每天两次重复给予200毫克酮康唑。单剂量酮康唑与稳态罗氟司特合用时，罗氟司特的AUC增加了34%；C(max)未改变。对于罗氟司特N - 氧化物，AUC和C(max)分别下降了12%和20%。重复剂量的酮康唑使罗氟司特的AUC和C(max)分别增加了99%和23%；对于罗氟司特N - 氧化物，AUC未改变，C(max)下降了38%。未观察到临床相关不良事件。酮康唑和罗氟司特合用时不需要调整罗氟司特的剂量。
