Bauer E, McDougall J, Cameron B D
Xenobiotica. 1986 Jul;16(7):625-33. doi: 10.3109/00498258609043552.
Isomerization of trans-4'-(2-hydroxy-3,5-dibromo-benzylamino)cyclohexanol (HDBC) in vivo has been investigated in horse, cow, dog, rat and man. Following oral administration of 4'-trans-HDBC to the horse, a very efficient first-pass trans-cis isomerization was observed. In the urine of the horse and cow, 40% and 29% respectively of the conjugated alcohols consisted of the 4'-cis isomer. Isomerization in rat and dog took place only to a small extent, and in man no 4'-cis isomer was detected. Oxidation of HDBC to the corresponding ketone, at pH 9.0, was highest with horse- and rat-liver 10 000 g supernatants and lowest with dog-liver supernatant. Reduction of the ketone with 10 000 g liver supernatants and with cryst. horse-liver alcohol dehydrogenase led to the formation of the alcohol containing 42-69% as the 4'-cis isomer, whereas after reduction with NaBH4 the alcohol contained only 20% of the 4'-cis isomer. This indicates that the conformer with the lower energy (1' and 4' position equatorially substituted) preferentially formed only during chemical reduction. A correlation between the formation of the ketone in vitro and the formation of 4'-cis-HDBC in vivo was observed in the horse, cow and dog. No similar correlation was found in the rat, where a high in vivo trans-cis isomerization might have been expected from the in vitro data.
已在马、牛、狗、大鼠和人体中研究了反式-4'-(2-羟基-3,5-二溴苄基氨基)环己醇(HDBC)在体内的异构化情况。给马口服4'-反式-HDBC后，观察到非常高效的首过反式-顺式异构化。在马和牛的尿液中，分别有40%和29%的共轭醇由4'-顺式异构体组成。大鼠和狗体内的异构化程度很小，在人体中未检测到4'-顺式异构体。在pH 9.0条件下，HDBC氧化为相应的酮，以马肝和大鼠肝10000g上清液最高，以狗肝上清液最低。用10000g肝上清液和结晶马肝醇脱氢酶还原酮，生成的醇中4'-顺式异构体含量为42%-69%，而用NaBH4还原后，醇中4'-顺式异构体仅占20%。这表明能量较低的构象体(1'和4'位为平伏取代)仅在化学还原过程中优先形成。在马、牛和狗中观察到体外酮的形成与体内4'-顺式-HDBC的形成之间存在相关性。在大鼠中未发现类似的相关性，根据体外数据，预计大鼠体内会有较高的反式-顺式异构化。
