Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers

Polk, Ron E.; Healy, Daniel P.; Sahai, Jan; Drwal, L; Racht, Edward M.

doi:10.1128/aac.33.11.1841

Cited by 149 publications

(65 citation statements)

References 14 publications

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“…A classic example is the interference of milk (calcium), iron salts, and antacids containing polyvalent cations with tetracycline absorption (7). Similarly, the absorption of fluoroquinolones is considerably impaired in the presence of cations such as calcium, iron, magnesium, zinc, and aluminum (5,(10)(11)(12).…”

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confidence: 99%

Inhibition of norfloxacin absorption by dairy products

Kivistö

Ojala-Karlsson

Neuvonen

1992

Antimicrob Agents Chemother

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Seven healthy subjects received, after an overnight fast, a single 200-mg oral dose of norfloxacin with water, whole milk, and unflavored yoghurt. Coadministration of milk or yoghurt reduced the extent of norfloxacin absorption and the mean peak concentration in plasma by approximately 50%. Taking of norfloxacin with these liquid dairy products should be avoided.Food-drug interactions have been studied extensively in recent years, but because of the complex nature of these interactions, general guidelines for clinical practice cannot be given (8,15). Food can influence drug absorption by a wide variety of mechanisms, resulting in changes in both the rate and the extent of bioavailability. The formation of poorly absorbed chelate complexes is one important mechanism of absorption interactions. A classic example is the interference of milk (calcium), iron salts, and antacids containing polyvalent cations with tetracycline absorption (7). Similarly, the absorption of fluoroquinolones is considerably impaired in the presence of cations such as calcium, iron, magnesium, zinc, and aluminum (5, 10-12).Concurrent ingestion of food with fluoroquinolones has been shown not to interfere with their absorption to a clinically significant degree (4,6,14). For example, Frost and coworkers (1) found that the bioavailability of ciprofloxacin is unaffected by a breakfast containing a high amount of calcium. However, we recently demonstrated (9) that the bioavailability of ciprofloxacin is significantly reduced when it is taken together with 300 ml of milk or yoghurt. To our knowledge, the effects of dairy products on the absorption of other fluoroquinolones have not been studied. The objective of this study was to characterize the effects of two liquid dairy products, whole milk and unflavored yoghurt, on the absorption of norfloxacin.A randomized, three-period, crossover design was used. Each treatment period was separated by a 7-day washout period. Four male and three female volunteers, aged 19 to 24 years and weighing 55 to 90 kg and considered healthy on the basis of medical history, physical examination, and routine laboratory tests, participated in the study. The volunteers were thoroughly informed in writing, and verbal consent was obtained. The study protocol was approved by the ethics committee of the Turku University Medical School.After an overnight fast, the subjects ingested 200 mg of norfloxacin (one 200-mg Lexinor tablet; Astra Pharmaceuticals, Sodertalje, Sweden) with 300 ml of water, 300 ml of whole milk (Valio, Helsinki, Finland), or 300 ml of unflavored yoghurt (Valio). The temperature of water, milk, and yoghurt was 12 to 14°C at the time of administration. The milk and yoghurt portions contained 360 and 450 mg of calcium, 9.6 and 11.4 g of protein, 11.7 and 7.5 g of fat, and 14.1 and 15 g of carbohydrates, respectively. The subjects were allowed to undertake their normal daily activities immediately after receiving the norfloxacin dose; fasting was continued for 3 h. Blood samples for the norfloxacin assay * ...

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confidence: 99%

Inhibition of norfloxacin absorption by dairy products

Kivistö

Ojala-Karlsson

Neuvonen

1992

Antimicrob Agents Chemother

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“…Therefore, the 50-90% reductions in urinary excretion of norfloxacin observed in this study following concurrent ingestion of several preparations containing metal ions may be associated with a decreased efficacy of norfloxacin in the treatment of urinary tract and systemic infections. The bioavailability of other quinolone antimicrobials has been shown to be less when they are ingested with antacid or mineral preparations (Kara et al, 1991;Nix et al, 1989b) and binding of metal ions contained in these preparations to the 4 keto and 3 carboxyl groups of quinolones is likely to be responsible Polk et al, 1989). As these chemical groups are common to additional quinolone antimicrobials it is probable that metal ions will have a similar effect on their bioavailability.…”

Section: Discussionmentioning

confidence: 99%

“…A variety of pharmaceuticals containing metal ions have been shown to interfere with the absorption of another quinolone antimicrobial, ciprofloxacin (Kara et al, 1991;Nix et al, 1989b;Polk et al, 1989). It has also been reported that aluminium containing preparations alone or with magnesium interfere with norfloxacin bioavailability possibly because of the formation of non-absorbable norfloxacin-metal ion complexes (Nix et al, 1989a).…”

Section: Introductionmentioning

confidence: 99%

Norfloxacin interaction with antacids and minerals.

Campbell

Kara

Hasinoff

et al. 1992

Brit J Clinical Pharma

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The urinary excretion of norfloxacin was measured in eight healthy volunteers after its co-administration with a variety of over-the-counter preparations, each containing a different metal ion. Commonly used doses of ferrous sulphate, zinc sulphate, aluminium hydroxide and magnesium hydroxide reduced the 24 h urinary excretion of norfloxacin by 50 to 90%. Bismuth subsalicylate had no significant effect. In vitro experiments demonstrated the formation of complexes between norfloxacin and iron, zinc, aluminium, and magnesium ions, respectively. Many pharmaceuticals contain the same metal ions that caused significant interactions with norfloxacin. The efficacy of norfloxacin treatment may be compromised when it is taken concurrently with preparations containing these metal ions.

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“…There are convincing reports that the impairment of the absorption of ciprofloxacin by metal cations is as a result of the formation of a water soluble, non-absorbable metal chelate complex with the 3-carboxyl and 4 keto oxygen groups of the ciprofloxacin molecule which are in close proximity [23,24] thus resulting in very low lipophilicity leading to poor permeation through the gut wall [1,6,17]. The presence of cations in the leaves of C. papaya may be sufficient in impairing the absorption of ciprofloxacin.…”

Section: Discussionmentioning

confidence: 99%