title: Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate.
abstract: In an open, randomized, triple crossover study, the effects of cisapride and sucralfate on the pharmacokinetics of sparfloxacin were assessed. Fifteen healthy volunteers received 400 mg of sparfloxacin as a single oral dose on day 0. In a random order, concomitant doses of 10 mg of cisapride three times daily from day -2 to day 2 and 1 g of sucralfate four times daily from day -2 to day 0 were administered. Sparfloxacin concentrations were measured by bioassay and high-performance liquid chromatography. Pharmacokinetic parameters for sparfloxacin alone were as follows (mean +/- standard deviation): maximum concentration of drug in serum (C(max)), 1.27 +/- 0.39 microg/ml; time to C(max) (T(max)), 4.1 +/- 1.9 h; area under the concentration-time curve (AUC), 35.0 +/- 9.7 microg x h/ml; mean residence time, 28.5 +/- 5.7 h; half-life (t1/2), 20 +/- 4 h; urinary recovery (UR x f), 11.0% +/- 2.7%; and metabolite-sparfloxacin ratio in urine, 2.6. For the cisapride group there was a significant decrease in the sparfloxacin T(max) (1.9 +/- 2.1 h) and a significant increase in C(max) (1.74 +/- 0.73 microg/ml). The QTc interval for patients receiving sparfloxacin and cisapride was prolonged by 7.7% compared to the QTc interval during medication-free periods. Significant differences in the values for the group receiving sucralfate compared to the values for the group receiving sparfloxacin alone were found: C(max), 0.77 +/- 0.31 microg/ml; AUC, 18.6 +/- 5.8 microg x h/ml; t1/2, 26 +/- 10 h; and UR x f, 5.8 +/- 1.8%. Concomitant adminstration of cisapride accelerates the absorption and increases the peak concentration of sparfloxacin without having a significant effect on the extent of bioavailability. Coadministration of sucralfate leads to a 44% decrease in the bioavailability of sparfloxacin.
authors.affiliation: Department of Pulmonary and Infectious Diseases, City Hospital Zehlendorf-Heckeshorn, Freie Universitat Berlin, Germany.
authors.forename: J A
authors.initials: JA
authors.lastname: Zix
authors.forename: H F
authors.initials: HF
authors.lastname: Geerdes-Fenge
authors.forename: M
authors.initials: M
authors.lastname: Rau
authors.forename: J
authors.initials: J
authors.lastname: Vöckler
authors.forename: K
authors.initials: K
authors.lastname: Borner
authors.forename: P
authors.initials: P
authors.lastname: Koeppe
authors.forename: H
authors.initials: H
authors.lastname: Lode
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D020117:Cisapride; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013392:Sucralfate / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D024841:Fluoroquinolones; D010880:Piperidines; D015363:Quinolones; D013392:Sucralfate; C061363:sparfloxacin; D020117:Cisapride