The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin

Aims To investigate the effect of sucralfate on sparfloxacin absorption whe n administered concurrently or at strategically spaced dosing times designe d to avoid the potential interaction. Methods The study was a four-way crossover design where eight healthy Japan ese volunteers were randomized to one of four treatment sequences at entry. A 300 mg dose of sparfloxacin was administered alone for treatment A (cont rol). Treatments B, C and D included sucralfate 1.5 g every 12 h for five d oses. For treatment B, the fifth dose of sucralfate was administered concur rently with sparfloxacin 300 mg. For treatment C, 300 mg sparfloxacin was g iven 2 h prior to the fifth dose of sucralfate. Treatment D consisted of sp arfloxacin 300 mg given 4 h prior to the fifth dose of sucralfate. Blood an d urine samples were collected at predetermined time intervals for 72 h. Sp arfloxacin concentrations in plasma and urine and the concentrations of spa rfloxacin metabolite in urine were determined by high performance liquid ch romatography assays. Results Sucralfate administrated concurrently with sparfloxacin decreased t he mean AUC(0, infinity) of sparfloxacin 2-fold ( P < 0.001) and the mean C -max 2.1-fold ( P < 0.001) compared with sparfloxacin alone. When sucralfat e was administrated 2 h after sparfloxacin, the mean AUC(0, infinity) was d ecreased 1.5-fold (P<0.01) and the mean C-max 1.4-fold (P<0.01). Sucralfate did not alter the extent of absorption of sparfloxacin when it was given 4 h after the administration of sparfloxacin. The relative bioavailabilities for treatments B, C and D were 0.50 (95% CI: 0.35-0.65), 0.64 (95% CI: 0.5 1-0.77), and 0.92 (95% CI: 0.81-1.03), respectively, relative to sparfloxac in alone. The mean percentage of the sparfloxacin dose recovered in urine w as significantly lower after sparfloxacin was administered with sucralfate than after sparfloxacin was administered alone or 2 h before the sucralfate dose (P<0.001). Treatments B, C and D were demonstrated to be equivalent t o treatment A in the rate of absorption. The t(max), CLr, and t(1/2) were n ot significantly affected by sucralfate. The metabolism of sparfloxacin was not altered in the presence of sucralfate. Conclusions Oral administration of sucralfate with sparfloxacin or 2 h afte r sparfloxacin, decreased the extent of sparfloxacin absorption. When bath, drugs are to be administered together, sucralfate should be administered 4 h after sparfloxacin, allowing thus sufficient time for sparfloxacin absor ption prior to the sucralfate dose and thereby minimizing the chance of a s ignificant interaction.