3,4-Dichlorobenzyloxyacetic acid is extensively metabolized to a taurine conjugate in rats.
The metabolism of the antisickling agent 3,4-dichlorobenzyloxyacetic acid (3,4-DCBAA) was examined after ip administration to rats. Within 5 days after administration of radiolabeled 3,4-DCBAA, 77.4 +/- 4.6% of the dose was recovered in the urine and only 3.2 +/- 0.5% was recovered in the feces. Metabolites in the urine were isolated and characterized by HPLC, electron impact MS, and LC/MS, and their identities were confirmed by comparing their spectra with those of synthetic standards. Quantitation of these urinary metabolites revealed that the majority of the radioactive dose was excreted as a taurine conjugate (60.1 +/- 4.4%), while lesser amounts were excreted as 3,4-dichlorohippurate, unchanged 3,4-DCBAA, the glycine conjugate of 3,4-DCBAA, and a polar unknown which is believed to be glycolic acid. A pathway involving an initial O-dealkylation at the benzyl carbon of 3,4-DCBAA and proceeding through the glycine conjugation of 3,4-dichlorobenzoic acid has been proposed to explain the formation of 3,4-dichlorohippurate and the polar unknown. The extensive conjugation of 3,4-DCBAA with taurine is an unprecedented observation in rats, which usually utilize glycine for amino acid conjugation reactions. Further studies with 3,4-DCBAA may provide insight into the enzymatic mechanisms of taurine conjugation, which are not well defined at this time.
D000755:Anemia, Sickle Cell / Q000188:drug therapy; D000818:Animals; D001192:Arylsulfatases / Q000494:pharmacology; D001593:Benzyl Compounds / Q000378:metabolism*; D005243:Feces / Q000032:analysis; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism*
D001593:Benzyl Compounds; D005965:Glucuronates; D013654:Taurine; C053061:3,4-dichlorobenzyloxyacetic acid; D001192:Arylsulfatases; D005966:Glucuronidase; D005998:Glycine