Abstract
To reevaluate steroid therapy in acute hepatic failure (AHF), the pharmacokinetics of plasma prednisolone (PSL) and endogenous hydrocortisone (Fk) were examined in five patients with AHF, treated with PSL in comparison with clinical courses. The results showed that the disapperances of PSL from blood were markedly delayed and significant levels of PSL were observed even 12 hours after the administrations, in the presence of advanced hepatic encephalopathy. However, in survival cases, these changes recovered toward normal, accompanying both clinical and functional improvements without .serious side effects. On the other hand, high concentrations of plasma PSL were observed in fatal cases without the improvement of encephalopathy. These results suggested that changes of PSL pharmacokinetics were dependent on the severity of the hepatocellular damages in AHF, and so initial doses and discontinuation or tapering of the drug doses should be decided on the basis of clinical courses, especially the grade of encephalopathy. Rapid tapering in dosage should be done to prevent the severe adverse effects and inhibition of liver regeneration, if the coma grade progressively deteriorated even during steroid therapy. Moreover, suppression of Fk normalized on recovery from clinical manifestations and improvements in liver functions.
The present pharmacokinetic data suggest that serial measurements of plasma PSL and Fk are very useful as a therapeutic index for steroid therapy in AHF.
