Abstract
The pramacokinetic behavior of four possible enantiomers of loxoprofen was investigated in the rat. Plasma levels of diastereomeric trans-alcohol metabolite after intravenous injection of 1' R-isomers were significantly higher than after equal doses of 1'S-isomers, while those of cis-alcohol after doses of 1' R-epimers were contrarily lower. In vitro protein binding study revealed that 1'-isomers of loxoprofen showed slightly higher affinity to both plasma and liver cytosol that 1'S-isomers. The enantiomeric contents of each alcohol metabolite in biological fluids after oral doses of racemate (loxoprofen sodium) in both the rat and man were quantified using capillary gas-chromatography linked with an electron ionization mass spectrometry. Alcohol metabolite of loxoprofen in rat plasma was exclusively counted as 2'S-isomers, i. e. trans-(1'R, 2'S)-and cis-(1'S, 2'S)-enantiomer, while minor amounts of their antipodes, i. e. trans-(1' S, 2'R)-and cis-(1' R, 2'R)-alcohol, were excreted in human urine.
