To assess whether or not concomitant omeprazole treatment influences the pharmacokinetics of lomefloxacin and ciprofloxacin, a randomized, double-blind four-way-crossover study was performed. Another objective was to compare the pharmacokinetics of lomefloxacin and ciprofloxacin. Twelve healthy volunteers participated. On days 1 to 4 of each study period, each of them took 20 mg of omeprazole or a placebo orally, and on day 4, each took 400 mg of lomefloxacin or 500 mg of ciprofloxacin orally. Blood and urine samples were collected and assayed for the quinolones by high-pressure liquid chromatography. The mean peak concentrations in plasma (C max ) and the areas under the curves (AUC), respectively, of lomefloxacin and ciprofloxacin, respectively, after prior treatment with placebo were 2.88 ؎ 0.73 (mean ؎ standard deviation) as against 2.60 ؎ 0.76 g/ml and 24.9 ؎ 3.13 as against 11.9 ؎ 1.89 g ⅐ h/ml, and 72.4% ؎ 5.10% as against 36.1% ؎ 7.50% of the doses of lomefloxacin and ciprofloxacin, respectively, were recovered from the urine. None of the pharmacokinetic parameters differed significantly after prior treatment with omeprazole compared with placebo. The C max of lomefloxacin was not significantly higher than that of ciprofloxacin, but lomefloxacin's AUC reached twice that of ciprofloxacin because of its significantly longer half-life in plasma (6.68 ؎ 1.94 as against 4.15 ؎ 0.92 h, respectively, P Յ 0.01). Concomitant therapy with omeprazole did not alter the pharmacokinetics of lomefloxacin or ciprofloxacin in these single-dose studies.The bioavailability of fluoroquinolone antimicrobial agents is markedly reduced by aluminum-magnesium-containing antacids (15,19,20,40) and the aluminum-containing mucousprotective drug sucralfate (13). On the other hand, histamine 2 receptor antagonists exert only minor effects on the pharmacokinetics of the quinolones. One study indicated that cimetidine diminishes the clearance of pefloxacin by inhibiting its hepatic biotransformation (41), and intravenously administered ranitidine led to a 40% reduction in the bioavailability of enoxacin (15), but the pharmacokinetics of ciprofloxacin and ofloxacin were not altered by coadministration of ranitidine per os (20,32).The present randomized, double-blind study was designed to determine the effect of omeprazole, a powerful inhibitor of gastric H ϩ /K ϩ -ATPase (26), on the pharmacokinetics of lomefloxacin and ciprofloxacin. In addition, the pharmacokinetics of the two quinolones, which were administered open labeled, were compared.(Results of this study were presented as a poster at the 18th International Congress of Chemotherapy, Stockholm, 1993 [43]). MATERIALS AND METHODSSubjects. Twelve healthy volunteers participated. Six were females, and six were males. Their mean age, height, weight, and creatinine clearance were 31.8 Ϯ 7.00 years, 1.75 Ϯ 0.09 m, 72.5 Ϯ 9.34 kg, and 112 Ϯ 15.5 ml/min/1.73 m 2 , respectively (means Ϯ standard deviations). Exclusion criteria were a regular use of medication within 4 weeks prior to the ...