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Abstract
The pharmacokinetics and protein-binding of orally administered prednisolone have been studied in seven patients with chronic liver disease and portosystemic shunts. The peak prednisolone serum concentration and the time of peak prednisolone concentration were similar to those found in normal subjects, indicating that there is no clinically significant first-pass metabolism of prednisolone. The elimination half-time and the extent of bioavailability of total prednisolone tended to be lower in the patients, and the extent of free, unbound prednisolone higher, but the differences were not statistically significant. The patients had a significantly lower serum protein-binding of prednisolone than the controls. Despite the decreased protein-binding in the patients, however, the results indicate that changes occur in the pharmacokinetics of prednisolone that tend to reduce the bioavailability of free, biologically active prednisolone towards that seen in healthy subjects. Reduction of the prednisolone dose is therefore not indicated in patients with portosystemic shunt and chronic liver disease, even in the presence of hypoalbuminemia.