Bioavailability of prednisolone in patients with intestinal malabsorption: the importance of measuring serum protein-binding.

Abstract

The effect of intestinal malabsorption on the oral bioavailability of prednisolone has been studied in six patients with celiac disease and in six patients with malabsorption of various etiologies, five of whom had undergone gut resections. The serum protein-binding of prednisolone was measured in five patients with celiac disease and hypoalbuminemia and in eight healthy controls. Compared with the controls, patients with celiac disease had a 22% lower peak serum prednisolone concentration (p less than 0.05) and a 16% smaller area under the time-concentration curve of total prednisolone (NS). The proportion of free prednisolone was 79% greater in patients with celiac disease (p less than 0.01), and the area under the time-concentration curve of free, biologically active prednisolone 53% larger (p less than 0.05). There were no significant differences in peak prednisolone concentration or area under the time-concentration curve between the controls and the other patients with malabsorption, who all had normal serum albumin concentrations. These results indicate that the absorption of prednisolone in patients with malabsorption is normal and that the apparently reduced bioavailability in celiac disease patients is more likely to be due to an increased volume of distribution secondary to hypoalbuminemia and reduced protein-binding.