Theophylline and warfarin interaction studies with grepafloxacin

被引:18
作者
Efthymiopoulos, C [1 ]
Bramer, SL
Maroli, A
Blum, B
机构
[1] Glaxo Wellcome Res & Dev Ltd, Div Clin Pharmacol, Greenford UB6 0HE, Middx, England
[2] Otsuka Amer Pharmaceut Inc, Rockville, MD USA
[3] Millard Fillmore Hosp, Buffalo, NY 14209 USA
关键词
D O I
10.2165/00003088-199700331-00008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Two phase I trials, each involving 16 healthy adult volunteers, were performed to investigate possible interactions between grepafloxacin and theophylline or warfarin. In the theophylline study, grepafloxacin 600mg was administered once daily for 10 days to 12 volunteers who were receiving a maintenance dose of theophylline. This dose of theophylline was designed to produce mean serum theophylline concentrations of 7.5 mg/L; 4 volunteers received theophylline plus placebo. Pharmacokinetic parameters of theophylline were determined before grepafloxacin treatment and on day 10 of grepafloxacin or placebo administration. Peak theophylline concentrations and the area under the concentration-time curve increased significantly during grepafloxacin treatment, and apparent total clearance of theophylline was reduced by approximately 50%. No changes were observed in the placebo group and theophylline appeared to have no effect on the pharmacokinetics of grepafloxacin. In the warfarin study, grepafloxacin 600mg was given once daily for 14 days to volunteers receiving a maintenance dose of warfarin. Warfarin was discontinued during the last 4 days of grepafloxacin administration. The pharmacodynamics of warfarin did not change after administration of grepafloxacin. Similarly, warfarin had no significant effect on the pharmacokinetics of grepafloxacin. We conclude that during treatment with grepafloxacin maintenance, doses of theophylline should be reduced by 50%, and we recommend that serum concentrations of theophylline be monitored during treatment with grepafloxacin. However, no dose adjustment is necessary for grepafloxacin when it is coadministered with theophylline, and dose adjustment does not seem to be required in concomitant treatment with grepafloxacin and warfarin.
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页码:39 / 46
页数:8
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