Effect of liver function on the metabolism of prednisone and prednisolone in humans.

The systemic availability of total prednisone and unbound prednisolone, and the urinary excretion of 6 beta-hydroxyprednisolone, were measured after an oral dose of prednisone and an i.v. dose of prednisolone in 22 patients covering a wide range of liver function (galactose elimination capacity ranging from 3.3 mg/min X kg body wt to 9.2 mg/min X kg body wt). The area under the plasma concentration versus time curves of prednisolone and of prednisone decreased with increasing galactose elimination capacity. This dependency of the steroid concentrations on liver function was attributed to a decreased metabolic clearance and not to an increased systemic availability of the steroid given p.o. in patients with impaired liver function. The fractional excretion and the fractional clearance of 6 beta-hydroxyprednisolone declined with decreasing metabolic clearance rate of prednisolone or with decreasing galactose elimination capacity. Thus, the enzymes involved in the 6 beta-hydroxylation are not spared as liver function declines, and the exposure to the biologically active unbound prednisolone is increased in patients with impaired liver function in relation to the amount of prednisone or prednisolone administered.