The relative bioavailability of single oral doses of prednisone with and without sucralfate administration was determined in 12 healthy male volunteers. Each subject participated in a randomized three-way cross-over study consisting of the following three phases: treatment A, prednisone given alone; treatment B, 2 days pretreatment with sucralfate with a concomitant dose of sucralfate administered with prednisone; and treatment C, 2 days pretreatment with sucralfate with a sucralfate dose administered 2 h after the oral prednisone dose. Plasma prednisolone concentrations (active moiety of prednisone) were determined by a specific and sensitive high-performance liquid chromatographic assay and unbound prednisolone concentrations were determined by equilibrium dialysis. Bioavailability was assessed by comparing the areas under the plasma prednisolone concentration-time curves as well as peak concentrations, time to peak concentration, elimination rate constant, and half-life. No significant differences were noted in any of the treatment phases for any of the parameters except for the time of peak concentration which was slightly delayed from 1.0 +/- 0.6 to 1.7 +/- 0.9 h when sucralfate was concomitantly administered with the prednisone. Thus, the data from this study indicate that sucralfate does not have a clinically significant effect on the bioavailability of orally administered prednisone. The use of these two drugs in combination does not result in an interaction requiring dosage regimen alteration.