Abstract
The influence of cyclosporin A (CsA) on the hepatic clearance of prednisone (HCP) was studied in isolated perfused livers of normal and chronic uremic rats perfused with a hemoglobin-free medium containing prednisone at an initial concentration of 635 +/- 129 micrograms/liter. Prednisone concentration was measured by a normal phase HPLC technique. Addition of CsA to the perfusate in livers of normal rats resulted in an increase of HCP by 38% from 10.8 +/- 2.4 to 14.9 +/- 3.4 ml/min/liver (p less than 0.01). In livers of uremic rats no effect was observed. Acute pretreatment with a large dose (120 mg) of CsA/kg/day ip for 1 day resulted in a 41% increase of HCP in livers of normal rats from 10.8 +/- 2.4 to 15.2 +/- 3.2 ml/min/liver (p less than 0.01). No effect was observed in livers of uremic rats. Chronic pretreatment with a CsA dose of 16 mg/kg/day ip continuously infused for 1 week reduced the HCP by 26% in livers obtained from normal rats and by 29% in livers of uremic rats, 10.8 +/- 2.4 to 8.0 +/- 1.7 ml/min/liver (p less than 0.01) and 14.7 +/- 1.1 to 10.4 +/- 1.2 ml/min/liver (p less than 0.01), respectively, whereas pretreatment with 7 mg/kg/day sc of CsA for 4 weeks resulting in blood CsA concentrations below 350 ng/ml had no influence.(ABSTRACT TRUNCATED AT 250 WORDS)
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