The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin.
OBJECTIVE
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 Cmax 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 Cmax 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 tmax, CLr and t1/2 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 both 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.
Kamberi
M
M
The Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita, Japan. marika@oita-med.ac.jp
Nakashima
H
H
Ogawa
K
K
Oda
N
N
Nakano
S
S
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D013392:Sucralfate / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D013392:Sucralfate; C061363:sparfloxacin