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

Aims To investigate the effect of sucralfate on sparfloxacin absorption when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction. Methods The study was a four-way crossover design where eight healthy Japanese volunteers were randomized to one of four treatment sequences at entry. A 300 mg dose of sparfloxacin was administered alone for treatment A (control). Treatments B, C and D included sucralfate 1.5 g every 12 h for five doses. For treatment B, the fifth dose of sucralfate was administered concurrently with sparfloxacin 300 mg. For treatment C, 300 mg sparfloxacin was given 2 h prior to the fifth dose of sucralfate. Treatment D consisted of sparfloxacin 300 mg given 4 h prior to the fifth dose of sucralfate. Blood and urine samples were collected at predetermined time intervals for 72 h. Sparfloxacin concentrations in plasma and urine and the concentrations of sparfloxacin metabolite in urine were determined by high performance liquid chromatography assays. Results Sucralfate administrated concurrently with sparfloxacin decreased the 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 sucralfate was administrated 2 h after sparfloxacin, the mean AUC(0, infinity) was decreased 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: 0.51-0.77), and 0.92 (95% CI: 0.81-1.03), respectively, relative to sparfloxacin alone. The mean percentage of the sparfloxacin dose recovered in urine was 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 to treatment A in the rate of absorption. The t(max), CLr, and t(1/2) were not 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 after 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 absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction.