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.