The effect of ferrous sulphate and sucralfate on the bioavailability of oral gemifloxacin in healthy volunteers.
Sucralfate is a cytoprotectant with antacid properties and ferrous sulphate is commonly prescribed for iron-deficiency anaemia. This open, randomized, single-dose, five-way crossover study investigated the effect of sucralfate and ferrous sulphate on the bioavailability of gemifloxacin, a novel fluoroquinolone antimicrobial. Twenty-seven healthy male volunteers received gemifloxacin, 320 mg p.o., alone, 3 h after sucralfate (2 g) or ferrous sulphate (325 mg), or 2 h before sucralfate or ferrous sulphate. Each subject received all five dosing regimens in random order with at least 6 days between regimens. Plasma samples collected up to 48 h after dosing with gemifloxacin, were assayed for gemifloxacin to determine pharmacokinetic parameters. Administration of gemifloxacin 3 h after sucralfate produced a marked decrease of 53% in the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-infinity), and a decrease of 69% in the maximal plasma concentration (Cmax). Administration of gemifloxacin 3 h after ferrous sulphate resulted in only a modest reduction of 11% in AUC0-infinity and of 20% in Cmax, which was not considered to be clinically significant. In contrast, at the doses used neither sucralfate nor ferrous sulphate altered gemifloxacin bioavailability when it was administered 2 h before either of these agents. Gemifloxacin was well tolerated in all the regimens. The results of this study support the dosing recommendation that gemifloxacin can be safely administered at least 2 h before sucralfate or ferrous sulphate, or at least 3 h after ferrous sulphate.
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn, Herts, UK. Ann_Allen@sbphrd.com
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Allen
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Bygate
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Faessel
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Isaac
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Lewis
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005296:Ferrous Compounds / Q000494:pharmacology*; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D012016:Reference Values; D013392:Sucralfate / Q000494:pharmacology*
D000890:Anti-Infective Agents; D005296:Ferrous Compounds; D024841:Fluoroquinolones; D009287:Naphthyridines; C020748:ferrous sulfate; D013392:Sucralfate; D000077735:Gemifloxacin