Comparison of urinary excretion of pravastatin and temocapril in bile duct-ligated rats and Eisai hyperbilirubinemic rats (EHBR).
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.
Takada
Yukiko
Y
Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga-Cho, Itabashi-ku, Tokyo 173-8605, Japan.
Tachizawa
Hidetaka
H
Kurihara
Hiroko
H
Takayanagi
Motoe
M
Sasamoto
Takahiro
T
Akashi
Masahiro
M
Aiso
Mitsuhiko
M
Takamori
Yoriyuki
Y
Sano
Naoyo
N
Takikawa
Hajime
H
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*
D013841:Thiazepines; C069156:temocaprilat; C055603:temocapril hydrochloride; D017035:Pravastatin