Enzyme-inductive effect of a hypolipidemic compound N-bis-(p-chlorophenoxy)-acetyl-urea in man and rat.
Besides its antilipidaemic effect, the new clofibric acid derivative (N-bis-(p-chlorohenoxy)-acetyl-urea) has an enzyme-inductive effect. The drug was administered (100 mg/kg orally) to male, Wistar rats for three days. The treatment raised the weight of the liver, the content of liver microsomal protein and cytochrome p-450 and shortened the hexobarbital sleeping time. The increase of cytochrome p-450 dependent biotransformation was found by in vitro methods in 9000-g supernatant of liver homogenate. There was a growth in biotransformation of substrates of type I (ethylmorphine, aminopyrine) and an extreme increase in reduction of nitrobenzene. We did not find any change in biotransformation of the type-II substrate aniline. In 16 patients suffering from Gilbert's syndrome, there was a decrease in the level of serum bilirubin, and increase of D-glucuric-acid output in urine and bromsulphophthalein transport maximum following the treatment of this drug given in 150 mg/day orally for three weeks. After this treatment, the level of gamma-glutamyl-transpeptides did not change. The authors highly recommend the serious consideration of metabolic interaction during the clinical application.
D000293:Adolescent; D000328:Adult; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D005878:Gilbert Disease / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012890:Sleep / Q000187:drug effects
D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; D002994:Clofibrate; D010634:Phenobarbital