Reference

Species differences in metabolism of sodium 2-[4-(2-oxocyclopentylmethyl)phenyl]propionate dihydrate (loxoprofen sodium), a new antiinflammatory agent

Species differences in metabolism of sodium 2-[4-(2-oxocyclopentylmethyl)phenyl]propionate dihydrate (loxoprofen sodium), a new antiinflammatory agent. Tanaka, Yorihisa; Nishikawa, Yuko; Hayashi, Ryozo (Anal. Metab. Res. Lab., Sankyo Co., Ltd., Tokyo 140, Japan). Chem. Pharm. Bull., 31(10), 3656-64 (English) 1983. CODEN: CPBTAL. ISSN: 0009-2363. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Urinary metabolites of 14C-labeled loxoprofen [68767-14-6] were detd. in rats, mice, dogs and monkeys after oral administration of the drug. In all these animal species, the cyclopentanone moiety of loxoprofen was predominantly reduced to trans-OH (an active principle), together with cis-OH (minor product). The monohydroxy metabolites were further hydroxylated in rats to the diols, which were excreted in urine as the main metabolites. Mice excreted the monohydroxy metabolites mainly as their free forms. In dogs, the monohydroxy metabolites were conjugated with taurine and glucuronic acid, and monkeys furnished the ester glucuronides of the monohydroxy metabolites.In this experiment, several chemicals are used like 88378-22-7 and 88378-21-6 Thus, species differences were obsd. both in the hydroxylation and in the conjugation reactions of the monohydroxy metabolites produced by the redn. of loxoprofen. .

Optical inversion of (2R)- to (2S)-isomers of 2-[4-(2-oxocyclopentylmethyl)phenyl]propionic acid (loxoprofen), a new antiinflammatory agent, and its monohydroxy metabolites in the rat

Optical inversion of (2R)- to (2S)-isomers of 2-[4-(2-oxocyclopentylmethyl)phenyl]propionic acid (loxoprofen), a new antiinflammatory agent, and its monohydroxy metabolites in the rat. Nagashima, Hisomu; Tanaka, Yorihisa; Watanabe, Hidetoshi; Hayashi, Ryozo; Kawada, Katsuro (Anal. Metab. Res. Lab., Sankyo Co., Ltd., Tokyo 140, Japan). Chem. Pharm. Bull., 32(1), 251-7 (English) 1984. CODEN: CPBTAL. ISSN: 0009-2363. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Enantiomer ratios of 2-[4-(2-oxocyclopentylmethyl)phenyl]propionic acid (loxoprofen)(I) [68767-14-6] and its monohydroxy metabolites in plasma of rats were detd.Several substances with their cas registry numbers 76299-18-8 and 89631-49-2 may be metioned in this study. by high-performance liq. chromatog. after derivatization with the chiral reagent (1S)-1-(4-dimethylaminonaphthalen-1-yl)ethylamine [89631-49-2]. The ratios of (2S)- to (2R)-isomers of the parent acid and of 2-[4-(trans-2-hydroxycyclopentylmethyl)phenyl]propionic acid (trans-alc.) increased rapidly with time after oral administration of racemic and (2R)-loxoprofen [89675-46-7], while the (2S)-configuration remained completely intact after dosing with (2S)-isomer. The results clearly indicate that occurrence of irreversible optical inversion of (2R)- to (2S)-loxoprofen [89675-45-6] in rats. The administration of trans- and cis-alcs. showed that: (1) the optical inversion also occurs in these monohydroxy metabolites; and (2) the cis-alc. is easily converted to the trans-alc. through the parent acid, but the latter is not converted to the former. .