Peffer R C, Abraham D J, Zemaitis M A, Wong L K, Alvin J D
Drug Metab Dispos. 1987 May-Jun;15(3):305-11.
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.
在给大鼠腹腔注射抗镰变剂3,4-二氯苄氧基乙酸（3,4-DCBAA）后，对其代谢情况进行了研究。给予放射性标记的3,4-DCBAA后5天内，77.4±4.6%的剂量在尿液中回收，仅3.2±0.5%在粪便中回收。通过高效液相色谱法（HPLC）、电子轰击质谱法（EI-MS）和液相色谱-质谱联用（LC/MS）对尿液中的代谢产物进行分离和表征，并通过将其光谱与合成标准品的光谱进行比较来确认其身份。对这些尿液代谢产物的定量分析表明，大部分放射性剂量以牛磺酸共轭物的形式排出（60.1±4.4%），而较少的量以3,4-二氯马尿酸、未变化的3,4-DCBAA、3,4-DCBAA的甘氨酸共轭物以及一种据信是乙醇酸的极性未知物的形式排出。有人提出了一条涉及3,4-DCBAA苄基碳上初始O-脱烷基化并通过3,4-二氯苯甲酸的甘氨酸共轭作用的途径来解释3,4-二氯马尿酸和极性未知物的形成。3,4-DCBAA与牛磺酸的广泛共轭作用在大鼠中是前所未有的观察结果，大鼠通常利用甘氨酸进行氨基酸共轭反应。对3,4-DCBAA的进一步研究可能会深入了解牛磺酸共轭作用的酶促机制，目前这些机制尚不清楚。
