title: Stereoselective disposition of hydratropic acid in rat.
abstract: The stereoselective distribution, metabolism, and excretion of 2-phenylpropionic acid (hydratropic acid, HTA) was studied by giving racemic HTA (20 mg/kg) to intact, bile duct-cannulated, bile duct-ligated, and nephrectomized and bile duct-cannulated rats. In intact rats, the percentage of (R)-(-)-HTA in plasma was 53%, but 46-48% in various tissues at 5 min after dosing. A slightly higher binding affinity of (R)-(-)-HTA to plasma protein than the (S)-(+) form should be one of the important factors controlling the enrichment of (S)-(+)-HTA percentage in tissues and the increase of (R)-(-)-HTA percentage in plasma shortly after administration of racemate. About 66% of the dose was excreted in urine of intact rats (HTA acyl glucuronide (HTA-G): 54%; HTA: 12%) in 8 hr. Bile duct-cannulated rats excreted about 51% of the dose in bile as HTA-G and 40% in urine (HTA-G: 32%; HTA: 8%) in 6 hr. The (R)-(-)-enantiomer percentage of biliary HTA-G was about 25%, urinary HTA-G was 45%, and HTA was 57%. Since about 63% of the dose was excreted in bile and urine as the (S)-(+)-enantiomer after injection of racemate to bile duct-cannulated rats, stereoselective isomerization of (R)-(-)-HTA to the (S)-(+) form is suggested. The (R)-(-)-enantiomer percentage of HTA-G in urine decreased with ligation of the bile duct, but that of the HTA-G in 0-30-min bile was not influenced by nephrectomy. These results suggest that the step regulating stereoselective excretion of HTA-G in rats is that of its excretion from the liver into bile and blood. There should be no or very little stereoselectivity in the step of HTA-G excretion through the kidney into the urine.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D008297:Male; D010666:Phenylpropionates / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013237:Stereoisomerism
chemical_list: D001798:Blood Proteins; D005965:Glucuronates; D010666:Phenylpropionates; C013025:hydratropic acid