title: Comparison of urinary excretion of pravastatin and temocapril in bile duct-ligated rats and Eisai hyperbilirubinemic rats (EHBR).
abstract: OBJECTIVE
  In patients with complete bile duct obstruction, the only pathway for the elimination of cholephilic compounds is through the urine. Although changes in various transporters in the liver and kidney in cholestasis have been elucidated, little is known about how effectively the elimination of these compounds is compensated for by urinary excretion.
  
  
  METHODS
  In the present study, the urinary excretion of pravastatin and temocapril was studied in bile-duct-ligated rats (BDLR) for 3 days and in Eisai hyperbilirubinemic rats (EHBR). After urinary bladder cannulation, radiolabeled pravastatin and temocapril were injected intravenously. Urine samples were collected every 1 h for 4 h, and the radioactivity was counted.
  
  
  RESULTS
  Urinary excretion of pravastatin was markedly increased in BDLR (85.9% of the dose after 4 h) and moderately increased in EHBR (35.9% of the dose after 4 h) compared with that in control rats (5.5% of the dose after 4 h). Similar but less prominent differences were observed with temocapril after it was administered (50.7%, 38.2%, and 22.0% of the dose after 4 h in BDLR, EHBR, and the controls, respectively).
  
  
  CONCLUSIONS
  The absence of biliary excretion of anionic drugs was compensated for by urinary excretion in BDLR and EHBR, and the compensation was more efficient with pravastatin than with temocapril. In patients with complete bile duct obstruction, the only pathway for the elimination of cholephilic compounds is through the urine. Although changes in various transporters in the liver and kidney in cholestasis have been elucidated, little is known about how effectively the elimination of these compounds is compensated for by urinary excretion.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga-Cho, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takada
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Tachizawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kurihara
authors.forename: Motoe
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sasamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Akashi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Aiso
authors.forename: Yoriyuki
authors.initials: Y
authors.lastname: Takamori
authors.forename: Naoyo
authors.initials: N
authors.lastname: Sano
authors.forename: Hajime
authors.initials: H
authors.lastname: Takikawa
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002779:Cholestasis / Q000652:urine*; D004195:Disease Models, Animal; D006932:Hyperbilirubinemia / Q000652:urine*; D008297:Male; D017035:Pravastatin / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000652:urine*
chemical_list: D013841:Thiazepines; C069156:temocaprilat; C055603:temocapril hydrochloride; D017035:Pravastatin