Document Detail


Lauramide diethanolamine absorption, metabolism, and disposition in rats and mice after oral, intravenous, and dermal administration.
MedLine Citation:
PMID:  8818565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The disposition of carbon-14-labeled lauramide diethanolamine (LDEA) was determined in rats after iv, dermal, and oral administration, and in mice after iv and dermal administration. Intravenous doses of LDEA to rats and mice (25 and 50 mg/kg, respectively) were mostly excreted in the urine (ca. 80-90%), with only about 10% excreted in the feces 72 hr after dosing. No unchanged LDEA, diethanolamine, or diethanolamine-derived metabolites were detected in urine. LDEA concentrated to the highest levels in the adipose tissue, and was only very slowly cleared from that tissue. Residues were also observed in liver and kidney, but clearance from those tissues paralleled the decreases in blood concentrations. Incubations of LDEA with liver slices from rats and humans showed that the compound is well absorbed by hepatic tissue from both species. LDEA was readily converted to metabolites found in vivo in rats, as well as other metabolites that are potentially intermediate products formed after omega- and/or omega-1 to 4 hydroxylation. Treatment with diethylhexylphthalate, an inducer of cytochrome P4504A1, which catalyzes the omega-hydroxylation of lauric and other fatty acids, demonstrated the involvement of that isozyme in the hydroxylation of LDEA. Dermally applied LDEA, at doses of 25 and 400 mg/kg to rats, was moderately (25-30%) well absorbed. Repeat administration (25 mg/kg/day for 3 weeks) did not change the rate of LDEA absorption. The absorption of 100 mg/kg doses was studied in jugular vein-cannulated rats. Steady state levels of LDEA equivalents were reached 24 hr after dermal administration. LDEA comprised about 15% of the radioactivity in plasma, with the remainder present as polar metabolites. A range of 50-70% of the dermal doses to mice, applied at 50, 100, 200, and 800 mg/kg, was absorbed in 72 hr. Absorbed LDEA distributed into the tissues with the same relative profile as that for the iv dose, except that distribution into adipose tissue was considerably lower. High oral doses of LDEA (100 mg/kg) in rats were well absorbed and mostly excreted in the urine as two very polar metabolites. The metabolites were isolated and characterized as the half-acid amides of succinic and of adipic acid, presumably arising from omega-hydroxylation and eventual beta-oxidation to give the chain-shortened products.
Authors:
J M Mathews; K deCosta; B F Thomas
Related Documents :
11758635 - Absorption, distribution, metabolism and excretion of [14c]levocetirizine, the r enanti...
420145 - Steady-state turnover and body pool of ascorbic acid in man.
1441595 - Stereoselective inhibition of nortriptyline hydroxylation in man by quinidine.
6817765 - Pharmacokinetics and biotransformation studies of terfenadine in man.
2573495 - Disposition, metabolism, and excretion of u-71038, a novel renin inhibitor peptide, in ...
7660445 - Development of resistance to chloroquine by plasmodium vivax in myanmar.
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  24     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-03-31     Completed Date:  1997-03-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  702-10     Citation Subset:  IM    
Affiliation:
Center for Bioorganic Chemistry, Research Triangle Institute, RTP, NC 27709, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Absorption
Adipose Tissue / metabolism
Administration, Cutaneous
Administration, Oral
Alkane 1-Monooxygenase
Animals
Cytochrome P-450 Enzyme System / metabolism
Diethylhexyl Phthalate / pharmacology
Ethanolamines / metabolism*,  pharmacokinetics*,  urine
Humans
Injections, Intravenous
Kidney / metabolism
Lauric Acids / metabolism*,  pharmacokinetics*,  urine
Liver / metabolism
Male
Mice
Mixed Function Oxygenases / metabolism
Rats
Rats, Inbred F344
Grant Support
ID/Acronym/Agency:
N01-ES-15329/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Ethanolamines; 0/Lauric Acids; 117-81-7/Diethylhexyl Phthalate; 120-40-1/lauric acid diethanolamide; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC 1.14.15.3/Alkane 1-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Replacing 14C with stable isotopes in drug metabolism studies.
Next Document:  First-pass metabolism of lidocaine in the anesthetized rabbit. Contribution of the small intestine.