1. The effect of ferrous sulphate (300 mg), ferrous gluconate (600 mg), and a combination tablet of iron (10 mg), magnesium (100 mg), zinc (15 mg), calcium (162 mg), copper (2 mg), and manganese (5 mg) (Centrum Forte) co‐administration on ciprofloxacin bioavailability was tested in eight healthy subjects. 2. Peak serum ciprofloxacin concentrations and area under the curve (AUC) were significantly reduced when ciprofloxacin was administered with 300 mg ferrous sulphate (3.0 vs 2.0 mg l‐1, P less than 0.05 and 12.3 vs 6.7 mg l‐1 h, P less than 0.01, respectively). Reductions in peak ciprofloxacin concentrations and AUC also occurred when ciprofloxacin was ingested with 600 mg ferrous gluconate (1.3 mg l‐1, P less than 0.01 and 4.1 mg l‐1 h, P less than 0.01, respectively) and a Centrum Forte tablet (1.4 mg l‐1, P less than 0.01 and 5.4 mg l‐1 h, P less than 0.01, respectively). 3. When ferrous ion was mixed with ciprofloxacin, rapid spectral changes occurred (t1/2 = 1.9 min). Additional studies were consistent with oxidation of the ferrous form of iron to its ferric form, which is followed by rapid formation of a Fe(3+)‐ciprofloxacin complex. Ciprofloxacin seems to bind to ferric ion in a ratio of 3:1 by interacting with the 4‐keto and 3‐carboxyl groups on ciprofloxacin. 4. The formation of a ferric ion‐ ciprofloxacin complex is probably the cause of the reduction in ciprofloxacin bioavailability in the presence of iron.

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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1. This study examined the effects of administering ferrous sulphate 325 mg with Sinemet (100/25 tablet) on levodopa and carbidopa bioavailability and on signs of Parkinson's disease in nine patients. 2. Ferrous sulphate ingestion with Sinemet resulted in a decrease in levodopa area under the curve (AUC) of 30% (P less than 0.01) and a greater than 75% decrease in carbidopa AUC. Despite a strong relationship between reductions in levodopa AUC and reductions in Sinemet efficacy (r = 0.83, P less than 0.01), the average reduction in Sinemet's efficacy associated with ferrous sulphate did not achieve statistical significance (P = 0.055). 3. Chemical studies indicate that iron forms chemical complexes with carbidopa in a similar manner to levodopa and is a likely mechanism for the drug interactions. 4. AUC when a Sinemet tablet is taken concurrently with a ferrous sulphate tablet appears to be clinically significant in some but not all patients. The clinical significance of repeated ingestion of ferrous sulphate with Sinemet requires further studies.