The metabolic chiral inversion of 2-phenylpropionic acid in rat, mouse and rabbit.
The metabolic chiral inversion of the 2-arylpropionic acids has been investigated in laboratory animals, using the simplest congener, 2-phenylpropionic acid, as a model compound. The chiral inversion was found to occur after administration of the racemate to the rat and rabbit, but not in the mouse. The formation of the ester glucuronide was enantioselective for the S-(-)-isomer in the rat and mouse, but showed no stereoselectivity in the rabbit. [corrected]  In the rat, the extent of inversion from R-(-) to S-(+) was greater at a dose of 30 mg/kg than at 150 or 300 mg/kg. The enantiomeric composition of the acid in urine was the same when the racemate was given orally or by i.p. injection. When the R-(-)isomer was given to rats, some 30% of the excreted acid was in the S-(+)-form, but when the S-(+)-isomer was given, the inversion was much less evident. In this case, the S/R ratio of the excreted phenylproprionic acid was ca 9:1. Following the administration of the racemate to rats, the plasma elimination half-life of the R-(-)-form was shorter (3.0 vs 4.8 hr for the S-(-)-isomer); this was due to its considerably greater plasma clearance (65.9 vs 43.6 micrograms/ml hr), since the volumes of distribution of the enantiomers were the same. The S/R ratio of 2-phenylpropionic acid in plasma rose progressively with time, from 1:1 in the dose solution to 2.1:1 at 8 hr.
D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D010666:Phenylpropionates / Q000008:administration & dosage / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism
D002250:Carbon Radioisotopes; D005965:Glucuronates; D010666:Phenylpropionates; C013025:hydratropic acid