Corticosteroids in liver disease: studies on the biological conversion of prednisone to prednisolone and plasma protein binding.
The conversion of prednisone to the biologically active corticosteroid prednisolone and the degree of plasma protein binding of prednisolone were studied in 22 patients with acute or chronic liver disease and in eight control subjects. In patients whose disease was active at the time of study, as judged by elevated serum levels of bilirubin and transaminase, significantly higher levels of plasma prednisolone were obtained after prednisolone administration than after equivalent doses of prednisone. In addition, the amount of unbound drug in the plasma was higher in patients with active disease. There was a significant correlation between the extent of plasma protein binding of prednisolone and the serum albumin concentration. Azathioprine did not affect the plasma binding of prednisolone in vitro. The plasma half-life of prednisolone was prolonged in two of three patients with chronic liver disease studied. These results suggest that in patients with acute hepatitis or active chronic liver disease there is impairment of reduction of the 11-oxo group of prednisone, and also impaired ring A reduction of prednisolone. Thus, incomplete conversion of prednisone to prednisolone occurs, which is a necessary step for biological activity; on the other hand there is also impairment of prednisolone degradation. These, together with low serum albumin concentrations which are associated with higher levels of circulating unbound prednisolone, result in quite different levels of biologically active corticosteroids compared with equivalent doses of prednisone or prednisolone in subjects without liver disease. The findings have important practical implications for the use of corticosteroids in patients with active liver disease.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D001711:Biotransformation; D001798:Blood Proteins; D001806:Blood Urea Nitrogen; D005260:Female; D006505:Hepatitis / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000097:blood / Q000378:metabolism*; D011241:Prednisone / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors; D014316:Tritium
D001798:Blood Proteins; D012709:Serum Albumin; D014316:Tritium; D011239:Prednisolone; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001379:Azathioprine; D001663:Bilirubin; D011241:Prednisone