The effect of uremia upon the hepatic clearance rate of prednisone was studied in isolated perfused livers of normal and uremic female rats. The perfusion rate was kept at a constant flow rate of 25 ml/min. In order to induce uremia, one group of rats was 5/6 nephrectomized 3 weeks prior to the perfusions. The concentrations of prednisone and other steroids were measured by a normal phase HPLC technique. In experiments with an initial prednisone concentration of 500-700 micrograms/l, the hepatic clearance rate of prednisone was significantly (p less than 0.001) increased by 40% in livers obtained from uremic rats (11.1 +/- 0.49 ml/min/liver) as compared to control rats (8.0 +/- 1.17 ml/min/liver). No significant correlation was found between the hepatic clearance rate of prednisone and increasing initial prednisone concentrations from 141 to 1,953 micrograms/l in the perfusate. It is concluded that an adaptive mechanism may exist in uremia which results in an increase of the hepatic clearance rate of prednisone.
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Egfjord et al. (2008) studied this question.