DMD Celsis microsomes equal better data

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


     

This Article
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Koster, A. S.
Right arrow Articles by Noordhoek, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koster, A. S.
Right arrow Articles by Noordhoek, J.

Glucuronidation of morphine and six beta 2-sympathomimetics in isolated rat intestinal epithelial cells

AS Koster, AC Frankhuijzen-Sierevogel and J Noordhoek

The metabolism of morphine and six beta 2-sympathomimetics (orciprenaline, terbutaline, fenoterol, salbutamol, ritodrine, and bamethan) in isolated rat intestinal epithelial cells was investigated. Only conjugates with glucuronic acid were detected. With regard to observed Vmax values the beta 2-sympathomimetics can be divided in two groups. The three resorcinols (orciprenaline, terbutaline, fenoterol) have a Vmax value comparable to that of morphine (70-230 pmol/min X mg cell protein). The phenolic beta 2-sympathomimetics (salbutamol, ritodrine, bamethan) exhibit a Vmax value comparable to the Vmax value of 1-naphthol (500-1100 pmol/min X mg cell protein). Calculation of intestinal intrinsic (metabolic) clearance and intestinal first pass extraction ratios from Vmax and Kappm values suggests that most of these drugs may undergo substantial intestinal first pass metabolism after oral administration. The glucuronidation of morphine in isolated mucosal cells could be completely inhibited by addition of 1-naphthol (50 microM), salicylamide (5 mM), or fenoterol (5 mM). Glucuronidation of fenoterol could be partially inhibited by 1-naphthol, salicylamide, and morphine. Preliminary data obtained with microsomes suggest that 1- naphthol and morphine are metabolized by different forms of the intestinal microsomal UDP-glucuronosyltransferase. Fenoterol and ritodrine are probably glucuronidated by the form, which also glucuronidates morphine. The results demonstrate that rat intestinal epithelial cells can be used to predict intestinal metabolism of morphine and other drugs at least qualitatively and that phenolic food constituents (e.g. 1-naphthol) and non-prescription drugs (e.g. salicylamide) may affect the intestinal first pass metabolism of morphine and fenoterol.

Volume 13, Issue 2, pp. 232-238, 03/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
K. S. Pang
MODELING OF INTESTINAL DRUG ABSORPTION: ROLES OF TRANSPORTERS AND METABOLIC ENZYMES (FOR THE GILLETTE REVIEW SERIES)
Drug Metab. Dispos., December 1, 2003; 31(12): 1507 - 1519.
[Full Text] [PDF]


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

Copyright © 1985 by the American Society for Pharmacology and Experimental Therapeutics.