Clearance of prednisone in isolated perfused livers of normal and uremic rats. Effects of acute and chronic cyclosporin A administration.
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)
Egfjord
M
M
Medical Department P, Rigshospitalet, Copenhagen, Denmark.
Daugaard
H
H
Olgaard
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008111:Liver Function Tests; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011241:Prednisone / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000378:metabolism*
D003524:Cyclosporins; D011241:Prednisone