The effects of milk and yogurt on the bioavailability of ciprofloxacin were studied in seven healthy volunteers in a randomized crossover trial. After an overnight fast, 500 mg ciprofloxacin was given with 300 ml water, milk, or yogurt. Plasma ciprofloxacin concentrations were significantly (p < 0.05) lower during the milk and yogurt phases from ½ to 10 hours; at ½ hour the concentration was reduced by 70% by milk and by 92% by yogurt. Milk reduced the peak plasma concentration by 36% (p < 0.05) and yogurt by 47% (p < 0.05). The extent of bioavailability, measured as the total area under the plasma concentration‐time curve and 24‐hour urinary excretion of ciprofloxacin, was reduced by 30% to 36% by milk and yogurt (p < 0.05). We conclude that the absorption of ciprofloxacin can be reduced by concomitant ingestion of milk or yogurt. To avoid therapeutic failures in infections where the causative organism is only moderately susceptible, ingestion of large amounts of dairy products in liquid form with ciprofloxacin is not recommended. Clinical Pharmacology and Therapeutics (1991) 50, 498–502; doi:

The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin and ofloxacin was studied in three separate, two-period crossover trials, each involving eight healthy volunteers. After an overnight fast, a single dose of norfloxacin (400 mg), ciprofloxacin (500 mg) or ofloxacin (400 mg) was administered with and without ferrous sulphate (corresponding to 100 mg elemental iron). The absorption of all the fluoroquinolones studied was significantly reduced when they were co-administered with ferrous sulphate. The reduction in the area under the plasma drug concentration-time curve from 0 to 24 h was most marked in the case of norfloxacin, while ofloxacin was least affected by ferrous sulphate. The AUC of norfloxacin was reduced by 73% (P < 0.001) and its peak plasma concentration by 75% (P < 0.01) by concomitant ingestion of ferrous sulphate. The AUC and peak plasma concentration of ciprofloxacin were reduced by 57% (P < 0.001) and 54% (P < 0.01), respectively, by ferrous sulphate. Concomitant ingestion of ferrous sulphate reduced the AUC and peak plasma concentration of ofloxacin by 25% (P < 0.01) and 36% (P < 0.01), respectively. Similar results were obtained with respect to the urinary recoveries of each fluoroquinolone. We recommend that norfloxacin and ciprofloxacin should not be taken together with ferrous sulphate. It would also be advisable not to take ofloxacin with ferrous sulphate, especially if the organism causing infection is only moderately susceptible.

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...

The effects of different cation containing products on the absorption of lomefloxacin were evaluated in eight healthy volunteers in a five-way randomized crossover study. The treatments were lomefloxacin alone, lomefloxacin with milk (300 ml), lomefloxacin with calcium carbonate (corresponding to 500 mg calcium), lomefloxacin with ferrous sulfate (corresponding to 100 mg elemental iron), and lomefloxacin with sucralfate (1 gm). Treatments were separated by a 7-day washout period. The bioavailability of lomefloxacin was significantly reduced when it was given with sucralfate; the area under the plasma drug concentration-time curve (AUC) from 0 to 24 hours was reduced by 51% (p < 0.05). Ferrous sulfate reduced the maximum plasma concentration of lomefloxacin by 26% (p < 0.05), the total amount of lomefloxacin recovered in urine by 15% (p < 0.05), and the AUC by 13% (p = 0.26). Calcium carbonate and milk had no significant effects on the bioavailability of lomefloxacin. We conclude that concomitant use of lomefloxacin and sucralfate should be avoided. It may also be advisable not to take lomefloxacin with ferrous sulfate, although this interaction is probably of no clinical significance. Calcium carbonate and milk do not affect lomefloxacin absorption.

Simultaneously administered magnesium hydroxide or sodium bicarbonate can increase the rate and extent of absorption of non-micronized glibenclamide and glipizide. To clarify the mechanism of this interaction we have studied the effect of pH on the dissolution of two different formulations of glibenclamide (micronized and non-micronized) and one formulation of glipizide. One tablet of each sulphonylurea preparation was placed in a dissolution chamber containing continuously mixed dissolution medium at pH 2, pH 6 or pH 9; 5 mL of the medium was replaced every 2 min. The amount of glibenclamide dissolved from the non-micronized formulation within 2 h, was 1.2, 4.5 and 76% at pH 2, pH 6 and pH 9, respectively (P < 0.01), whereas 21, 29 and 100% was dissolved from the micronized formulation (P < 0.01). The amount of glipizide dissolved within 2 h at pH 2, pH 6 and pH 9 was 3.9, 24 and 92%, respectively (P < 0.01). We conclude that the elevated pH of the gastric contents is the most likely explanation for the interactions previously demonstrated between antacids and sulphonylureas after their concomitant ingestion.