Pj Neuvonen

Interference of dairy products with the absorption of ciprofloxacin

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.

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

1. The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2. A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a non-micronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3. Magnesium hydroxide accelerated (P less than 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4. Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P less than 0.05), the total area three-fold (P less than 0.05) and the peak drug concentration three-fold (P less than 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P less than 0.05) and the maximum insulin response 10-fold (P less than 0.05) by magnesium hydroxide. 5. Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide.

Enhancement of absorption and effect of glipizide by magnesium hydroxide

The effects of magnesium hydroxide on the pharmacokinetics and pharmacodynamics of glipizide were studied in eight healthy volunteers in a randomized crossover trial. After an overnight fast, 5 mg glipizide was given with either 150 ml water or water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the areas under the plasma glipizide concentration‐time curves (AUC) from 0 to ½ hour and from 0 to 1 hour by 180% (p < 0.05) and 69% (p < 0.05), respectively. The peak plasma concentration, time to peak, total AUC, elimination half‐life, and mean residence time of glipizide remained unchanged. The incremental plasma insulin area from 0 to ½ hour increased by 85% (p < 0.05), and the time to maximal insulin response was reduced (p < 0.05) during the magnesium hydroxide phase. The corresponding decremental plasma glucose area increased fourfold (p < 0.05), and the maximal glucose decrease was 35% greater (p < 0.05) than during the control phase. We conclude that the concomitant ingestion of magnesium hydroxide and glipizide may result in accelerated absorption of glipizide and increased early insulin and glucose responses.

Milk and yoghurt do not impair the absorption of ofloxacin.

The effects of milk and yoghurt on the oral absorption of ofloxacin were studied in seven healthy volunteers in a randomized cross-over trial. After an overnight fast, 200 mg ofloxacin was given with 300 ml water, milk or yoghurt. Plasma concentrations and urinary excretion of ofloxacin were determined up to 24 h. Values of total plasma AUC and 24 h urinary excretion of ofloxacin were not affected by milk or yoghurt. Plasma ofloxacin concentrations from 0.5 to 1.5 h and the peak concentration were lower (P less than 0.05) after yoghurt than without and the time to peak was prolonged by 1 h (P less than 0.05).

Prevention of Chloroquine Absorption by Activated Charcoal

1 The ability of activated charcoal to prevent the absorption of chloroquine was investigated in healthy volunteers, and the effect of the charcoal-chloroquine ratio on the completeness of binding was studied in vitro. 2 After an overnight fast, six subjects ingested 500 mg of chloroquine phosphate with water, and another group of six subjects ingested 25 g of charcoal suspension within 5 min of chloroquine intake. The concentrations of chloroquine in plasma and whole blood were measured by high-performance liquid chromatography for 192 h. 3 Activated charcoal reduced the areas under the plasma and whole blood chloroquine concentration-time curves (AUC) from 0 to 192 h, the total AUCs, and the peak concentrations by 99% (P < 0.001). 4 Chloroquine was very effectively bound by activated charcoal in vitro, even at low charcoal-chloroquine ratios. For example, at a ratio of 5:1, about 98% of chloroquine was bound. 5 Activated charcoal should be very effective in reducing the absorption of that fraction of chloroquine dose which is in the stomach at the time of charcoal administration. Because the acute toxicity of chloroquine is extremely high and death usually occurs within 1-3 h of overdosage, charcoal should be given as early as possible in suspected chloroquine intoxication.

Effect of Activated Charcoal on the Absorption of Amiodarone

1 The ability of activated charcoal to prevent the absorption of amiodarone was studied in 18 healthy volunteers, divided into three groups of six subjects. 2 All subjects were administered a single dose of 400 mg amiodarone; one group ingested the drug with water only (control) and the second with 25 g of activated charcoal as a water suspension. The subjects in the third group were given 25 g of charcoal immediately after the 1.5 h blood sample. 3 The extent of amiodarone absorption was reduced by about 98% by simultaneously administered charcoal (P < 0.001); taking charcoal 1.5 h after amiodarone still resulted in a 50% reduction in amiodarone bioavailability (P < 0.05). 4 These results indicate that activated charcoal should be effective in preventing amiodarone absorption in acute poisoning.

Failure of Oral Activated Charcoal to Accelerate the Elimination of Amiodarone and Chloroquine

1 The effect of activated charcoal on the elimination of amiodarone and chloroquine was studied in the rat. 2 The study consisted of two separate experiments. Amiodarone and chloroquine were injected subcutaneously at doses of 200 mg kg-1 and 100 mg kg-1, respectively. Six rats in both experiments were put on a charcoal-containing diet 48 h after drug administration, while the control groups remained on a normal diet. 3 Treatment with repeated oral activated charcoal had no effect on the true elimination of amiodarone and chloroquine. 4 These results suggest that, after the distribution of amiodarone and chloroquine into peripheral compartments, their rate of elimination cannot be significantly accelerated with multiple oral doses of activated charcoal.