RT Journal Article SR Electronic T1 Stereoselective disposition of hydratropic acid in rat. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 614 OP 619 VO 13 IS 5 A1 T Yamaguchi A1 Y Nakamura YR 1985 UL http://dmd.aspetjournals.org/content/13/5/614.abstract AB 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.