DeLong A F, Smyth R D, Polk A, Nayak R K, Martin G, Douglas G H, Reavey-Cantiwell N H
Drug Metab Dispos. 1977 Mar-Apr;5(2):122-31.
Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis.
芬氯酸（α，间二氯-对环己基苯乙酸二乙铵盐）是一种新型非甾体抗炎药，大鼠、狗、猴和人经口服14C标记化合物溶液后，能迅速且定量地从胃肠道吸收。放射色谱法和质谱分析表明，在所有物种的吸收和消除阶段，芬氯酸都是血浆中的主要成分。同时也存在少量间氯-对环己基苯乙醇酸代谢物。芬氯酸及其代谢物主要局限于全血的血浆相中，并与血清白蛋白广泛结合。血浆消除半衰期因物种而异，在大鼠中为1.6小时，在狗中为6.5小时。主要分布组织为肝脏、肾脏和小肠。在任何组织隔室中均未发现药物或代谢物有明显的蓄积或潴留。芬氯酸在经尿液和胆汁消除之前已完全生物转化。在人和猴中，主要消除途径为肾脏，在狗中为胆汁。芬氯酸代谢物的肠肝循环在大鼠中被证实存在。主要尿代谢物为芬氯酸的羟基环己基类似物和间氯-对环己基苯乙醇酸。在正常大鼠和佐剂诱导的多关节炎大鼠中，芬氯酸的代谢和生物处置没有差异。
