[Conjugation reactions of ciprofibrate with human and laboratory animals].
An open problem of the lipid lowering agent ciprofibrate (rac-2-[4-(2,2-dichlorocyclopropyl)-phenoxy]-2-methylpropanoic acid, CAS 52214-84-3) is its metabolism concerning the conjugation with amino acids and glucuronic acid. It could be solved by syntheses of the needed reference compounds--unknown up to now--and administration of ciprofibrate to volunteers and rats. Unexpectedly the conjugation compounds with amino acids are stable in vitro and in metabolism. There was no evidence for any conjugation reaction with amino acids by investigating samples of urine and faeces. On the contrary the urine of humans contains 90-97% of beta-O-acylglucuronide, whereas rat urine shows only 10% of the calculated amount.
Oelschläger
Herbert
H
Biologisch-Pharmazeutische Fakultät, Friedrich-Schiller-Universität Jena, Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, 07743 Jena, Germany. b8oehe@rz.uni-jena.de
Müller
Dieter
D
Hellwich
Karl-Heinz
KH
Ueberall
Sieglinde
S
Seeling
Andreas
A
Machts
Heike
H
Hofmann
Brit
B
Glöckner
Reinhild
R
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine; D004355:Drug Stability; D005243:Feces / Q000737:chemistry; D058607:Fibric Acids; D020723:Glucuronic Acid / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism / Q000652:urine; D006801:Humans; D006868:Hydrolysis; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics* / Q000652:urine; D013058:Mass Spectrometry; D051381:Rats
D000596:Amino Acids; D058607:Fibric Acids; D020719:Glucuronides; D000960:Hypolipidemic Agents; D002995:Clofibric Acid; D020723:Glucuronic Acid; C019304:ciprofibrate