Twenty-six hospitalized patients participated in a randomized crossover study to evaluate the effect of enteral feedings on ciprofloxacin absorption when given orally or via gastrostomy or jejunostomy tubes. Patients in the oral group received an intact 500-mg ciprofloxacin tablet alone or ciprofloxacin plus three oral doses of Sustacal (240 ml given 8 h before, with, and 4 h after ciprofloxacin administration). Patients with gastrostomy or jejunostomy tubes received 500 mg of crushed ciprofloxacin in 60 ml water via the feeding tube. After a washout period, the patients received ciprofloxacin with a continuous enteral formula (Jevity) given at 60 to 90 ml/h beginning 6 h before drug administration and continuing for 10 h. Serial blood samples were analyzed for ciprofloxacin concentration by high-performance liquid chromatography. The maximum ciprofloxacin concentrations in serum for ciprofloxacin given and for ciprofloxacin plus enteral feeding for the oral, gastrostomy, and jejunostomy groups were (mean +/- standard deviation) 2.59 +/- 1.24 versus 1.43 +/- 0.61 micrograms/ml (P < 0.05), 3.68 +/- 1.36 versus 2.27 +/- 0.67 micrograms/ml (P < 0.05), and 3.78 +/- 1.87 versus 1.45 +/- 0.48 micrograms/ml (P < 0.05), respectively. Corresponding values for area under the concentration-time curve were 13.4 +/- 8.32 versus 9.44 +/- 4.74 micrograms/h/ml (P < 0.05) 15.9 +/- 6.62 versus 7.44 +/- 3.16 (micrograms/h/ml (P < 0.05), and 18.1 +/- 9.37 versus 5.82 +/- 2.63 micrograms.h/ml (P < 0.05). We conclude that enteral feedings given orally or via gastrostomy or jejunostomy tubes resulted in a 27 to 67% reduction in the mean bioavailability of ciprofloxacin in hospitalized patients. The decreased absorption may be clinically important, especially when the enteral feeding is coadministered with ciprofloxacin by the oral and jejunostomy tube routes. Reductions in maximum levels of ciprofloxacin in serum as a result of feedings given via a gastrostomy tube are similar to those following oral administration on an empty stomach, making a clinically important interaction by this route less likely.