Hopantenic acid beta-glucoside as a new urinary metabolite of calcium hopantenate in dogs.
The metabolism of calcium hopantenate (HOPA) was studied in beagle dogs. After oral administration of 14C-labeled HOPA, 25.5% of the administered radioactivity was excreted in the urine within 24 hr, mostly in the form of unchanged drug. The only metabolite, accounting for 4.2% of the radioactivity in the urine, was isolated by HPLC. The metabolite was hydrolyzed by the treatment of beta-glucuronidase (Helix pomatia), acid phosphatase, or beta-glucosidase. These enzyme activities were not inhibited by treatment with D-glucaric acid 1,4-lactone or PO4(3-), but with D-gluconic acid 1,5-lactone, demonstrating that the metabolite is a glucose conjugate. The compound was identified as HOPA-glucoside, 4'-O-(beta-D-glucopyranosyl)-D-hopantenic acid, by GC/MS analyses after derivatization of the metabolite and the synthetic compound. This is the first reported instance of glucose conjugation to a non-acidic hydroxyl group in the metabolism of xenobiotics in mammals.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005243:Feces / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine
C051025:hopantenic acid glucoside; C016030:pantogab; D010205:Pantothenic Acid; D005680:gamma-Aminobutyric Acid