DMD

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

0090-9556/04/3201-10-19$20.00
DMD 32:10-19, 2004

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kasumov, T.
Right arrow Articles by Brunengraber, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasumov, T.
Right arrow Articles by Brunengraber, H.

NEW SECONDARY METABOLITES OF PHENYLBUTYRATE IN HUMANS AND RATS

Takhar Kasumov, Laura L. Brunengraber, Blandine Comte, Michelle A. Puchowicz, Kathryn Jobbins, Katherine Thomas, France David, Renee Kinman, Suzanne Wehrli, William Dahms, Douglas Kerr, Itzhak Nissim, and Henri Brunengraber

Departments of Nutrition (T.K., L.L.B., B.C., M.A.P., K.J., K.T., F.D., R.K., H.B.) and Pediatrics (R.K., W.D., D.K.), Case Western Reserve University, Cleveland, Ohio; and Children's Hospital (S.W.) and Department of Pediatrics (I.N.), University of Pennsylvania, Philadelphia, Pennsylvania

Phenylbutyrate is used to treat inborn errors of ureagenesis, malignancies, cystic fibrosis, and thalassemia. High-dose phenylbutyrate therapy results in toxicity, the mechanism of which is unexplained. The known metabolites of phenylbutyrate are phenylacetate, phenylacetylglutamine, and phenylbutyrylglutamine. These are excreted in urine, accounting for a variable fraction of the dose. We identified new metabolites of phenylbutyrate in urine of normal humans and in perfused rat livers. These metabolites result from interference between the metabolism of phenylbutyrate and that of carbohydrates and lipids. The new metabolites fall into two categories, glucuronides and phenylbutyrate ß-oxidation side products. Two questions are raised by these data. First, is the nitrogen-excreting potential of phenylbutyrate diminished by ingestion of carbohydrates or lipids? Second, does competition between the metabolism of phenylbutyrate, carbohydrates, and lipids alter the profile of phenylbutyrate metabolites? Finally, we synthesized glycerol esters of phenylbutyrate. These are partially bioavailable in rats and could be used to administer large doses of phenylbutyrate in a sodium-free, noncaustic form.

Address correspondence to: Henri Brunengraber, Department of Nutrition, Room 280, Case Western Reserve University, 11000 Cedar Rd., Cleveland OH 44106-7139. E-mail: hxb8{at}cwru.edu






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2004 by the American Society for Pharmacology and Experimental Therapeutics.