THEOPHYLLINE AND WARFARIN INTERACTION STUDIES WITH GREPAFLOXACIN

Citation
C. Efthymiopoulos et al., THEOPHYLLINE AND WARFARIN INTERACTION STUDIES WITH GREPAFLOXACIN, Clinical pharmacokinetics, 33, 1997, pp. 39-46
Citations number
21
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
03125963
Volume
33
Year of publication
1997
Supplement
1
Pages
39 - 46
Database
ISI
SICI code
0312-5963(1997)33:<39:TAWISW>2.0.ZU;2-F
Abstract
Two phase I trials, each involving 16 healthy adult volunteers, were p erformed to investigate possible interactions between grepafloxacin an d theophylline or warfarin. In the theophylline study, grepafloxacin 6 00mg was administered once daily for 10 days to 12 volunteers who were receiving a maintenance dose of theophylline. This dose of theophylli ne was designed to produce mean serum theophylline concentrations of 7 .5 mg/L; 4 volunteers received theophylline plus placebo. Pharmacokine tic parameters of theophylline were determined before grepafloxacin tr eatment 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 app arent total clearance of theophylline was reduced by approximately 50% . No changes were observed in the placebo group and theophylline appea red 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 d iscontinued during the last 4 days of grepafloxacin administration. Th e pharmacodynamics of warfarin did not change after administration of grepafloxacin. Similarly, warfarin had no significant effect on the ph armacokinetics of grepafloxacin. We conclude that during treatment wit h grepafloxacin maintenance, doses of theophylline should be reduced b y 50%, and we recommend that serum concentrations of theophylline be m onitored during treatment with grepafloxacin. However, no dose adjustm ent is necessary for grepafloxacin when it is coadministered with theo phylline, and dose adjustment does not seem to be required in concomit ant treatment with grepafloxacin and warfarin.