Sucralfate significantly reduces ciprofloxacin concentrations in serum

The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations of pefloxacin and its metabolites in plasma and urine were determined by high-performance liquid chromatography assays. We found that coadministration of magnesium and aluminum hydroxide caused a decrease of levels of pefloxacin in plasma and urine. The area under the plasma concentration-time curve decreased significantly (P < 0.001), suggesting impaired absorption of pefloxacin from the gastrointestinal tract. The relative bioavailability of pefloxacin after the antacid treatment was 44.4% ± 23.8%, compared with that after a single administration. The underlying mechanism of this drug interaction is the formation of chelate complexes and probably also physical adsorption to the aluminum hydroxide gel. The metabolism of pefloxacin was not altered by the antacid treatment. Renal clearance was found to depend on urinary pH.Terminal half-life was significantly shorter after the antacid treatment, probably because of an increase in nonrenal clearance. In conclusion, pefloxacin should be given at least 2 h before the antacid to ensure sufficient therapeutic efficacy of the quinolone.Under clinical conditions, antacids may be administered together with the new quinolone antibacterial agents. Antacids are known to alter both absorption of drugs from the gastrointestinal tract and renal elimination (12). A decrease in the rate and extent of absorption of orally administered drugs by a concomitant antacid treatment may reduce drug activity considerably. Alteration of urinary pH may lead to changes in renal excretion of acidic and basic drugs.In this investigation, the influence of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics and bioavailability of pefloxacin was evaluated. Pefloxacin is a newer quinolone carboxylic acid derivative with a broad spectrum of activity (3). A decrease in the bioavailability of several quinolones after concomitant intake of magnesium-aluminum hydroxide has recently been described elsewhere (5, 9, 13, 18, 19) and reviewed (4, 24). However, the extent of this interaction among individual quinolones, was quite different, which makes a prediction of the extent of the effect of the antacid on new derivatives difficult. Therefore, antacid-quinolone interaction studies are required for each newly developed quinolone. Pefloxacin differs from other quinolones in its extensive metabolism and in its considerable reabsorption in the kidney tubules (14). For that reason, an interaction with antacids at the hepatic and renal sites was also assessed in this study.

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confidence: 99%

Effect of an antacid containing magnesium and aluminum on absorption, metabolism, and mechanism of renal elimination of pefloxacin in humans

Jaehde

Sörgel

Stephan

et al. 1994

“…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.…”

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confidence: 95%

Interaction study of lomefloxacin and ciprofloxacin with omeprazole and comparative pharmacokinetics

Stuht¹,

Lode²,

Koeppe³

et al. 1995

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 ...

“…Sucralfate has been shown to decrease the absorption of, e.g., ciprofloxacin (3,15), norfloxacin (17), and fleroxacin (11). The bioavailability of ciprofloxacin and norfloxacin was reduced by about 90% when they were administered with sucralfate.…”

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confidence: 98%

Effect of sucralfate on absorption of norfloxacin and ofloxacin

Lehto

Kivistö

1994

The effect of sucralfate on the pharmacokinetics of norfloxacin and ofloxacin was assessed in two separate crossover studies with healthy volunteers. In both studies, eight subjects were randomized to one of the following three regimens: a 400-mg dose of norfloxacin or ofloxacin alone, norfloxacin or ofloxacin given simultaneously with sucralfate (1 g), or norfloxacin or ofloxacin given 2 h before sucralfate. Coadministration of sucralfate reduced the bioavailability of norfloxacin and ofloxacin by 91% (P < 0.001) and 61% (P < 0.001), respectively. However, when norfloxacin and ofloxacin were given 2 h before sucralfate, there were no significant alterations in the pharmacokinetics of either fluoroquinolone. Similar results were obtained when the cumulative amount of each fluoroquinolone recovered in the urine was used to calculate bioavailability. To avoid these interactions and potential therapeutic failures, norfloxacin and ofloxacin should not be used concurrently with sucralfate. The interaction can be minimized by maximizing the time between the fluoroquinolone dose and the previous sucralfate dose and giving the fluoroquinolone at least 2 h before another sucralfate dose.Antacids and sucralfate are known to impair the absorption of fluoroquinolone antimicrobial agents from the gastrointestinal tract by formation of nonabsorbable chelate complexes (1-4, 10, 11, 15-17). Sucralfate has been shown to decrease the absorption of, e.g., ciprofloxacin (3, 15), norfloxacin (17), and fleroxacin (11). The bioavailability of ciprofloxacin and norfloxacin was reduced by about 90% when they were administered with sucralfate. However, coadministration of fleroxacin with sucralfate only slightly decreased the absorption of the former. To our knowledge, there is no published study on the effect of sucralfate on the absorption of ofloxacin.It has been demonstrated that the interaction with sucralfate can be decreased by staggering the administration times of sucralfate and a fluoroquinolone (15, 17). However, in these studies, sucralfate was given before the fluoroquinolone dose, which may not be the best approach. In addition to the length of the interval separating the intake of a fluoroquinolone and a drug containing cations, the sequence in which the drugs are ingested is important.The purposes of this investigation were to study the effect of sucralfate on the absorption of ofloxacin and norfloxacin and to determine whether probable interactions could be prevented by giving the fluoroquinolone dose 2 h before sucralfate. MATERIALS AND METHODSSubjects and study design. Two separate randomized threeperiod crossover studies were performed. Treatments were separated by a 7-day washout period. A total of 16 volunteers were recruited to participate in this investigation. The subjects were determined to be healthy on the basis of medical history, physical examination, and laboratory tests. They were thoroughly informed in writing, and verbal consent was obtained. [Medipolar, Oulu, Finland]), or norfloxacin alone followed by...