Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation

The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period. Methods: Tablets of ciprofloxacin (500 mg), levofloxacin (500 mg), and ofloxacin (300 mg) were crushed and mixed with 240 mL of Ensure, water and calcium chloride (500 mg(L), water and magnesium chloride (200 mg/L), water and calcium chloride and magnesium chloride, and water alone. Fluoroquinolone concentrations of the mixtures were measured, via high-performance liquid chromatography, at baseline and serially over 24 hours. Experiments were performed in duplicate, at three temperatures (5 deg C, 25 deg C, and 37 deg C).

Results: Average decreases of 82.5% +/- 1.5% for ciprofloxacin, 61.3% +/- 5.2% for levofloxacin, and 45.7% +/- 10.1% for ofloxacin (mean +/- 95% CI) were observed in vitro for Ensure over the two experimental sets at baseline. Serial analysis revealed no further significant change in any of the quinolone concentrations over the remaining 24-hour period. No significant decrease was noted with the quinolones when mixed in water and calcium, water and magnesium, water and calcium and magnesium, or water alone. This phenomenon appears to be unaffected by time and temperature. Conclusions: These data suggest there is an immediate and significant loss of fluoroquinolone when mixed with Ensure. An explanation for the loss of fluoroquinolone remains unclear. (journal of Parenteral and Enteral Nutrition 24:42-48, 2000)



The use of enteral feeding formulations has increased in both the acute and long-term care settings. According to the revised American Society for Parenteral and Enteral Nutrition Critical Care Practice Guidelines, enteral feeding is the nutrition intervention of choice.1 Additionally, commercially available enteral feeding formulations Ge, Ensure; Ross Products Division, Abbott Laboratories, Columbus, OH) are becoming more frequently accessible for use on an ambulatory or outpatient basis. Direct consumer marketing of these products to the elderly population via print and television media encourages the outpatient use of enteral feeding formulations.

Oral fluoroquinolone antibiotics are particularly useful in home health care and long-term care settings. Characterized by favorable pharmacokinetic profiles, relatively few adverse drug reactions, and potent broad-spectrum activity, the quinolones remain one of the few oral anti-infective agents with activity against rapidly emerging multi-drug resistant pathogens.2 The difficulties of administering parenteral antibiotics on an outpatient basis along with economic pressure to switch to a more cost-effective oral agent for outpatient administration has increased fluoroquinolone use in these setting.3,4 Many of these patients, however, still have sufficient comorbidities to necessitate enteral feeding.

Because of the lack of commercial liquid antibiotic preparation and difficulty in dosing antibiotics around enteral feeding times, patients requiring continous enteral feedings have had flouroquinolone tablets crushed and mixed in their feedings.5 Additionally, ambulatory patients "washing down" fluoroquinolone tablets with Ensure or consuming both products within close proximity of one another on an outpatient basis is not an unrealistic scenario.

Recent in vivo research suggests a significant reduction in the oral bioavailability of ciprofloxacin and ofloxain when delivered with enteral feedings.4,6-9 Mueller and colleagues4 observed reduced relative bioavailabilities of ciprofloxacin (72% +/- 14%) and ofloxacin (90% +/- 8%) when coadministered with Ensure. Problems also have been reported between fluoroquinolone antibiotics and food,10-18 vitamins with iron,19-21 antacids,22-27 and sucralfate.28-30 The formation of nonabsorbable chelates with divalent cations at the 4-keto- and 3-carboxyl-groups of the quinolones has been suggested as the mechanism responsible for the reduced quinolone absorption.25,29-34 This has been demonstrated as clinically relevant, as treatment failures have been reported in the literature.5,35

In preliminary experimental work, we noted a decrease in levofloxacin concentrations when combined in vitro with Ensure. The diminished concentration was noticed immediately upon dissolution of the fluoroquinolone tablet in the Ensure matrix and did not appear to be temperature- or time-dependent (unpublished data).

In this study, we attempted to expand upon our initial findings. Our primary objective was to determine the percent loss of three commercially available fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin) when combined with a common enteral feeding formulation in vitro. To more accurately characterize the nature of this interaction, we examined the effects of time and temperature. Secondarily, because chelation interactions with divalent cations25,29-34 are the proposed mechanism for this interaction, we attempted to differentiate the effects of calcium and magnesium contained in Ensure in a similar fashion.


Refer: http://findarticles.com/p/articles/mi_qa3762/is_200001/ai_n8896431
by Wright, David H, Pietz, Sarah L, Knostantinides, Frank N, Rotschafer, John C