Document Detail

Cefpodoxime-proxetil hydrolysis and food effects in the intestinal lumen before absorption: in vitro comparison of rabbit and human material.
MedLine Citation:
PMID:  10477812     Owner:  NLM     Status:  Publisher    
The luminal and mucosal deesterification of the prodrug ester cefpodoxime-proxetil was studied in human duodenal washings in vitro. Enzymatic hydrolysis of the ester, releasing the active third generation cephalosporin, was observed in luminal washing in the same way as it had previously been observed in the rabbit. Eserine and PMSF and HgCl(2) were potent inhibitors of cefpodoxime-proxetil hydrolysis in luminal washing, suggesting the participation of a cholinesterase in the hydrolysis of cefpodoxime-proxetil. These results are in agreement with our previous findings performed in the rabbit. Moreover, cefpodoxime-proxetil directly decreases the acetylcholinesterase activity when tested by a specific enzymatic method. These observations support the hypothesis that the partial oral bioavailability of cefpodoxime-proxetil results from hydrolysis by luminal cholinesterases. In vitro experiments run with rabbit duodenal washing with food components were compared with the pharmacokinetics of cefpodoxime-proxetil in humans. Amino acids, trace elements and vitamins were potent inhibitors for cefpodoxime-proxetil hydrolysis in duodenal washings. Otherwise, lipids (LTC and mixed LCT/MCT) did not interact. In the human, cefpodoxime-proxetil bioavailability is significantly enhanced when tablets are administered with food. The correlation found between animal results and human results in vitro for prospective investigation of a new prodrug ester could be very useful. An in vitro hydrolysis in intestinal animal washings could allow the potentially degraded condition and the food effect of the luminal tract to be assessed before absorption.
Crauste-Manciet; Decroix; Farinotti; Chaumeil
Publication Detail:
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  157     ISSN:  1873-3476     ISO Abbreviation:  Int J Pharm     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1999-09-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  153-161     Citation Subset:  -    
Laboratoire de Pharmacotechnie et Dermopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Paris V, 4 av de l'Observatoire, 75006 Paris, France
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