Effect of oral adsorbent AST-120 on cyclosporin absorption in rats.
The oral adsorbent AST-120 is used to inhibit the progression of renal failure by adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is administered to patients receiving immunosuppressive medicines, it is important to study the effect of AST-120 on the amount of these and other drugs absorbed. We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and investigated the effect of oral administration of AST-120 on the absorption of cyclosporin in rats. The in-vitro adsorption ratios of AST-120 for cyclosporin were more than 80%. When pure cyclosporin powder was administered with AST-120, blood cyclosporin concentrations were significantly higher than when cyclosporin was administered alone. When cyclosporin dissolved in medium-chain triglyceride was administered to rats by intramuscular injection there was no significant difference in the blood cyclosporin concentration of rats given combined AST-120 and cyclosporin and those given cyclosporin alone. There was no significant difference between the serum concentration of total bile acids, in rats receiving combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving orally solely a solution of cyclosporin dissolved in olive oil. These results suggest that oral administration of AST-120 accelerates the absorption of orally administered cyclosporin from the gastrointestinal tract and does not affect the metabolism of cyclosporin. When a solution of cyclosporin in olive oil is administered orally, however, oral administration of AST-120 has no influence on cyclosporin absorption and does not affect the enterohepatic circulation of bile acids.
Takemoto
M
M
Department of Urology, Yamaguchi University School of Medicine, Japan.
Tsuchida
M
M
Konishi
M
M
Suga
A
A
Iojima
K
K
Naito
K
K
D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000327:Adsorption / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004042:Dietary Fats, Unsaturated / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008863:Microspheres; D000069463:Olive Oil; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D001647:Bile Acids and Salts; D004042:Dietary Fats, Unsaturated; D007166:Immunosuppressive Agents; D000069463:Olive Oil; D010087:Oxides; D010938:Plant Oils; D014280:Triglycerides; D002244:Carbon; D016572:Cyclosporine; C040896:AST 120