| The N-benzyl derivative of the glucosidase inhibitor 1-deoxynojirimycin shows a prolonged half-life and a more complete oral absorption in the rat compared with the N-methyl analog. | |
| | |
MedLine Citation:
|
PMID: 19570011 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Abstract The pharmacokinetic behavior of the glucosidase inhibitor and antiviral compound JV-benzyl-1-deoxynojirimycin (BndNM) was studied in rats in vivo and in isolated perfused livers. BndNM is a more lipophilic derivative of the glucosidase inhibitor A'-methyl-1-deoxynojirimycin (MedNM). This was reflected in the n-octanol/Krebs partition coefficients, which were 0.28 and 0.004, respectively. Compared with previously published data on the N-methyl analog, derivatization with the benzyl moiety caused an increase in both elimination half-life (from 32 min for MedNM to 69 min for BndNM) and steady-state distribution volume (164 mL for MedNM and 322 mL for BndNM) in vivo. The fraction of the dose excreted in urine after 2 h was decreased (66% for BndNM compared to 80% for MedNM), the fraction excreted in bile after 2 h was increased, both in vivo (1.5% of BndNM compared to 0.2% for MedNM) and in perfused livers (5% for BndNM compared to 0.5% for MedNM). Clearance decreased from 6.3 (MedNM) to 4.0 mL/min (BndNM). In unanesthetized rats, bioavailability of BndNM was found to be 100% after oral dosing. Fractionation of liver homogenates showed that BndNM was mainly present in the cytosolic fraction, with a slight accumulation in the lysosomal/endosomal fraction. The authors conclude that addition of the lipophilic phenyl group to the deoxynojirimycin backbone leads to more favorable pharmacokinetic properties of the glucosidase inhibitor. |
| | |
Authors:
|
E D Faber; L A van den Broek; E E Oosterhuis; B P Stok; D K Meijer |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Drug delivery Volume: 5 ISSN: 1071-7544 ISO Abbreviation: Drug Deliv Publication Date: 1998 |
Date Detail:
|
Created Date: 2009-07-02 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9417471 Medline TA: Drug Deliv Country: England |
Other Details:
|
Languages: eng Pagination: 3-12 Citation Subset: - |
Affiliation:
|
Department of Pharmacokinetics and Drug Delivery, University Centre for Pharmacy, Groningen Institute of Drug Studies [GIDS], Groningen, The Netherlands. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Fate of the predominant phospholipid component of DepoFoam(TM) drug delivery matrix after intratheca...
Next Document: Effect of pH on Drug Release from Polysaccharide Tablets.