Merdink J, Decosta K, Mathews J M, Jones C B, Okita J R, Okita R T
Department of Pharmaceutical Sciences, Washington State University, Pullman 99164-6510, USA.
Drug Metab Dispos. 1996 Feb;24(2):180-6.
Lauramide diethanolamine (LDEA)--a compound used in cosmetics and soap products as an emollient, thickener, and foam stabilizer--was observed to be metabolized by rat liver microsomes to two major products that were identified by GC/MS to be the 11-hydroxy and 12-hydroxy derivatives of LDEA. The specific activities for LDEA 11- and 12-hydroxylation in microsomes prepared from control rats were 2.23 +/- 0.40 and 0.71 +/- 0.17 nmol/min/mg protein, respectively. Treatment of rats with the cytochrome P4504A inducer and peroxisome proliferator, diethylhexyl phthalate, increased the LDEA 12-hydroxylation rate to 3.50 +/- 0.48 nmol/min/mg protein, a 5-fold increase in specific activity, whereas the LDEA 11-hydroxylase activity remained unchanged. Because LDEA contains a 12-carbon side chain, LDEA hydroxylation rates were compared with the hydroxylation rates for lauric acid. The specific activities of lauric acid 11- and 12-hydroxylation reactions in diethylhexyl phthalate-treated rats were 1.7-fold and 3.2-fold greater than the LDEA 11- and 12-hydroxylation rates, respectively. When LDEA hydroxylation reactions were performed in the presence of a polyclonal antibody to the rat P4504A forms, formation of 12-hydroxy-LDEA was inhibited by 80%. Rat kidney microsomes also supported the hydroxylation of LDEA at its 11- and 12-carbon atoms, with specific activities of 0.05 +/- 0.01 and 0.28 +/- 0.02 nmol/min/mg protein, respectively. LDEA was also metabolized to 11- and 12-hydroxy derivatives by human liver microsomes at specific activities of 0.22 +/- 0.06 and 0.84 +/- 0.26 nmol/min/mg protein, respectively.
月桂酰胺二乙醇胺（LDEA）——一种在化妆品和肥皂产品中用作润肤剂、增稠剂和泡沫稳定剂的化合物——被观察到可被大鼠肝微粒体代谢为两种主要产物，通过气相色谱/质谱法鉴定为LDEA的11-羟基和12-羟基衍生物。从对照大鼠制备的微粒体中LDEA 11-和12-羟基化的比活性分别为2.23±0.40和0.71±0.17 nmol/分钟/毫克蛋白质。用细胞色素P4504A诱导剂和过氧化物酶体增殖剂邻苯二甲酸二乙基己酯处理大鼠后，LDEA 12-羟基化速率增加到3.50±0.48 nmol/分钟/毫克蛋白质，比活性增加了5倍，而LDEA 11-羟化酶活性保持不变。由于LDEA含有一个12碳侧链，因此将LDEA羟基化速率与月桂酸的羟基化速率进行了比较。在邻苯二甲酸二乙基己酯处理的大鼠中，月桂酸11-和12-羟基化反应的比活性分别比LDEA 11-和12-羟基化速率高1.7倍和3.2倍。当在针对大鼠P4504A形式的多克隆抗体存在下进行LDEA羟基化反应时，12-羟基-LDEA的形成受到80%的抑制。大鼠肾微粒体也支持LDEA在其11-和12-碳原子处的羟基化，比活性分别为0.05±0.01和0.28±0.02 nmol/分钟/毫克蛋白质。人肝微粒体也将LDEA代谢为11-和12-羟基衍生物，比活性分别为0.22±0.06和0.84±0.26 nmol/分钟/毫克蛋白质。
