Abstract：
:Metronidazole (MTZ) is a drug of choice for protozoal infections such as luminal amoebiasis. We designed and synthesized N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-D,L-glycine (NMG) as a colon-specific prodrug of MTZ. The synthetic yield of NMG was about 34%. The apparent partition coefficient of MTZ was greatly reduced by the chemical modification. While (bio)chemically stable in the contents of the upper intestine, NMG was rapidly cleaved to liberate MTZ on incubation with the cecal contents of rats. MTZ metabolized quickly in the cecal contents at least partly by a microbial nitroreductase, suggesting that the metabolism of MTZ is relevant to its bioactivation leading to amoebicidal action. The systemic absorption, analyzed by the blood concentration and urinary recovery of NMG, was very low after oral administration of NMG. In parallel with this, whereas MTZ disappeared mostly during the transit of the proximal small intestine, a substantial amount of NMG remained in the small intestine moving down to the large intestine where it metabolized rapidly. Moreover, comparing systemic absorption of MTZ after oral administration of NMG or MTZ, NMG markedly reduced the systemic absorption. These results suggest that NMG is a potential colon-specific prodrug of MTZ which improves therapeutic and toxicological properties.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Kim D,Hong S,Jung S,Jung Y,Kim YMdoi
10.1002/jps.21720subject
Has Abstractpub_date
2009-11-01 00:00:00pages
4161-9issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(15)32940-3journal_volume
98pub_type
杂志文章abstract：:A pharmacokinetic model was developed describing the pharmacokinetics of stannous fluoride in human subjects after oral topical application of a stannous fluoride dentifrice. Twenty subjects participated in an investigation of an experimental dentifrice. Subjects rinsed their mouths with the experimental dentifrice sl...
journal_title：Journal of pharmaceutical sciences
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更新日期：2014-04-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600700733
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abstract：:The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid be...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600830327
更新日期：1994-03-01 00:00:00
abstract：:The objective of this study was to determine reasons behind the low oral (p.o.) bioavailability of glucosamine. By using male Sprague-Dawley rats, the movement of glucosamine through everted gut, the effect of dose and glucose, and inhibition of a glucose transporter (GLUT2) by quercetin were studied. Glucosamine phar...
journal_title：Journal of pharmaceutical sciences
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