Decrease of caffeine elimination in man during co-administration of 4-quinolones

Abstract

The single dose pharmacokinetics of caffeine (220–230 mg per dose) were investigated in 12 healthy male volunteers before and during treatment with ofloxacin (200 mg bd), ciprofloxacin (250 mg bd) and enoxacin (400 mg bd) with a cross-over study design. None of the parameters: mean elimination half-life (T_½cl), C_max, total body clearance (Cl_ωt) and the volume of distribution (αV_d) of caffeine were noticeably altered by administration of ofloxacin. Striking changes were observed, however, after administration of enoxacin: the T_½cl was prolonged by as much as 260%, the C_max increased by 41%; the aVd was reduced by 20% and Cl_ωt by 78% (mean values). Treatment with ciprofloxacin led to a prolongation of T_½cl by 15%, to a decrease of aVd by 25% and to a 33% decrease of Cl_ωt. The results of this intra-individual comparison of caffeine pharmacokinetic data demonstrate that treatment with ciprofloxacin and enoxacin may have a significant inhibitory effect on caffeine elimination.