Interaction study of lomefloxacin and ciprofloxacin with omeprazole and comparative pharmacokinetics

Abstract

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 ...

Effect of Omeprazole on the Pharmacokinetics of Oral Gemifloxacin in Healthy Volunteers

“…Co-administration of trovafloxacin and omeprazole reduced the AUC for trovafloxacin by 18% and the C max by 32% [12]. On the other hand, both AUC 0-∞ and C max for lomefloxacin showed small increases (5-8%) when given with omeprazole [21]. However, none of these changes are considered to be clinically important, and there are no recommendations to alter the dose of fluoroquinolones in the presence of omeprazole.…”

“…Both AUC 0-∞ and C max for ciprofloxacin decreased by 15-16% when administered with omeprazole [21]. Co-administration of trovafloxacin and omeprazole reduced the AUC for trovafloxacin by 18% and the C max by 32% [12].…”

“…Finally, about 80% of a given dose of omeprazole is excreted in the urine [18], and this may decrease the renal elimination of other substances. Small changes in the pharmacokinetic profiles of other fluoroquinolones have been observed following concomitant administration with omeprazole [12,21]; thus, it is important to investigate the potential effects of omeprazole on gemifloxacin.…”

Quinolones

“…Of interest, in vitro studies have demonstrated that enoxacin, cimetidine, ranitidine, and famotidine dissolution and availability for absorption in simulated gastric juice and simulated intestinal fluid are mutually reduced for all three enoxacin-histamine H 2 -receptor antagonist pairings [88]. Omeprazole has also not been shown to alter the pharmacokinetics of quinolones to a clinically-significant degree [56,[101][102][103]. Thus, these agents can be recommended as alternative noninteracting antiulcer and antiesophagitis therapy.…”

Gemifloxacin for the Treatment of Respiratory Tract Infections: In Vitro Susceptibility, Pharmacokinetics and Pharmacodynamics, Clinical Efficacy, and Safety

“…Omeprazole, a proton-pump inhibitor frequently prescribed for patients with peptic ulcers or other gastric acid-related conditions, has resulted in small changes in fluoroquinolone pharmacokinetics. 132,133 In theory, omeprazole interacts with other drugs by altering absorption due to decreasing gastric acid, altering clearance through occupying the CYP metabolic pathway, or competing for renal excretion. Thus, the impact of omeprazole on gemifloxacin pharmacokinetics was evaluated in a randomized, doubleblind, crossover study of 12 adult healthy male volunteers.…”