実験的腎臓障害ラットにおける薬物の生体内運命

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Blood concentration, tissue distribution, and excretion of drugs and drug-metabolizing enzyme activities were examined using ^<14>C-labeled compounds; 5,5-diphenylhydantoin (^<14>C-DPH) and 2-guanidinomethyl-1-monoazacyclooctane sulfate (^<14>C-EGYT-739) in male rats with a mercuric chloride-induced kidney injury. Carbon-14 radioactivity in blood of kidney-damaged rats was higher than that of the control, and the biological half-life of ^<14>C-DPH in blood was prolonged by kidney injury. Considerably high level of radioactivity was found in the kidney 24 hr after dosing, and the prolongation of half-life was also observed in the damaged kidney of rats. Urinary and fecal excretion of ^<14>C radioactivity were unchanged in kidney injury, whereas biliary excretion was significantly increased 6 to 24 hr after dosing of ^<14>C-EGYT-739,and slightly increased after dosing of ^<14>C-DPH. A single administration of mercuric chloride reduced aminopyrine demethylase and aniline hydroxylase activities in the liver, but did not change cytochrome P-450 and b_5 content. However, addition of mercuric chloride at a final concentration of 9.97×10^<-5>M to the microsomal suspension resulted in a partial conversion of cytochrome P-450 to cytochrome P-420.
公益社団法人日本薬学会の論文
1976-09-25