Increased clearance rate of prednisone in the isolated perfused liver of uremic rats.
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.
D000818:Animals; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005943:Gluconeogenesis; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D010101:Oxygen Consumption; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D011241:Prednisone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014511:Uremia / Q000378:metabolism*
D011241:Prednisone