On the metabolism of clofibride, a hypolipaemic drug.
The absorption and metabolism of clofibride, a new hypolipaemic drug of p-chlorophenoxyisobutyric type, were investigated in the CD rat, the beagle and the olive baboon monkey. Clofibride is rapidly and massively resorbed and hydrolysed into 4-chlorophenoxyisobutyric acid (CPIB) and 4-hydroxy-N-dimethylbutyramide (HMB). CPIB, in free and glucuroconjugated form, and its metabolite, 4-chlorophenol, in the form of the glucuronate ether, are found in the serum of the rat. HMB is rapidly metabolized. The half-life of CPIB, the main active metabolite, in the serum is about 12 h in the rat, 43 +/- 9 h in the dog and 6 +/- 1 h in the baboon. In the rat, peak hypocholesterolaemic activity occurs late--24 h after administration of the drug and 20 h after peak concentration of CPIB in the blood. The half-life of 4-chlorophenol glucuronate ether in the serum is about 4 h whereas that of HMB is about 3 h. In the rat, the elimination of clofibride takes place mainly via the urine since 70% of the dose administered is found in the form of free or conjugated CPIB, 10% in the form of HMB or one of its metabolites, in 48 h samples of urine. Over the same period, faecal elimination accounts for no more than 2% of the dose ingested. In addition, in this species, the CPIB, 30% of which is secreted via the biliary route without being eliminated in the faeces, undergoes an enterohepatic circulation.
D000284:Administration, Oral; D000577:Amides / Q000097:blood / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D004285:Dogs; D005260:Female; D005965:Glucuronates / Q000032:analysis; D006207:Half-Life; D000882:Haplorhini; D006868:Hydrolysis; D000960:Hypolipidemic Agents / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D010215:Papio; D051381:Rats; D013045:Species Specificity; D013997:Time Factors
D000577:Amides; D005965:Glucuronates; D000960:Hypolipidemic Agents; C007089:clofibride; D002994:Clofibrate