Linked Life Data

9756762

Source:http://linkedlifedata.com/resource/pubmed/id/9756762

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pubmed-article:9756762pubmed:dateCreated1998-11-9lld:pubmed
pubmed-article:9756762pubmed:abstractTextThe levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37 degreesC over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Delta2- and Delta3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Delta2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Delta3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t1/2s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers, t1/2s = 0.37 and 0.93 h; for the CPD diastereoisomers, t1/2s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t1/2 = 1.6 h; for the CPD t1/2 diastereoisomers, = 2.2 h). It is concluded that (i) the Delta2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Delta3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.lld:pubmed
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pubmed-article:9756762pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:9756762pubmed:articleTitleStability of cephalosporin prodrug esters in human intestinal juice: implications for oral bioavailability.lld:pubmed
pubmed-article:9756762pubmed:affiliationCLINPHARM SUPPORT GmbH, CH-4051 Basel, Switzerland. 100271,1114@compuserve.comlld:pubmed
pubmed-article:9756762pubmed:publicationTypeJournal Articlelld:pubmed
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