RT Journal Article
SR Electronic
T1 Hydroxylation of lauramide diethanolamine by liver microsomes.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 180
OP 186
VO 24
IS 2
A1 J Merdink
A1 K Decosta
A1 J M Mathews
A1 C B Jones
A1 J R Okita
A1 R T Okita
YR 1996
UL http://dmd.aspetjournals.org/content/24/2/180.abstract
AB 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.