Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution
The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 1989/09/25, Vol.37(9), pp.2369-2374 |
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| container_title | Chemical & pharmaceutical bulletin |
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| creator | MIYAUCHI, Masao SASAHARA, Kunihiro FUJIMOTO, Koichi KAWAMOTO, Isao IDE, Junya NAKAO, Hideo |
| description | The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein. |
| doi_str_mv | 10.1248/cpb.37.2369 |
| format | Article |
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II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution</title><source>J-STAGE Free</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>MIYAUCHI, Masao ; SASAHARA, Kunihiro ; FUJIMOTO, Koichi ; KAWAMOTO, Isao ; IDE, Junya ; NAKAO, Hideo</creator><creatorcontrib>MIYAUCHI, Masao ; SASAHARA, Kunihiro ; FUJIMOTO, Koichi ; KAWAMOTO, Isao ; IDE, Junya ; NAKAO, Hideo</creatorcontrib><description>The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.37.2369</identifier><identifier>PMID: 2605679</identifier><identifier>CODEN: CPBTAL</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Administration, Oral ; Buffers ; cefpodoxime proxetil ; cephalosporin ; Cephalosporins - administration & dosage ; Cephalosporins - chemical synthesis ; Cephalosporins - pharmacokinetics ; Chemical Phenomena ; Chemistry ; CS-807 ; Drug Stability ; Esters ; Exact sciences and technology ; isomerization ; kinetics ; Kinetics and mechanisms ; Organic chemistry ; Pentanoic Acids - administration & dosage ; Pentanoic Acids - chemical synthesis ; Pentanoic Acids - pharmacokinetics ; Phosphates ; prodrug ; Reactivity and mechanisms ; stability ; Δ2 cephalosporin</subject><ispartof>Chemical and Pharmaceutical Bulletin, 1989/09/25, Vol.37(9), pp.2369-2374</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4939-7d822b0dfbfa56bdad861a22fda64102d4c35f514f149c628bd2cb96c8ee22513</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27902,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6727966$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2605679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MIYAUCHI, Masao</creatorcontrib><creatorcontrib>SASAHARA, Kunihiro</creatorcontrib><creatorcontrib>FUJIMOTO, Koichi</creatorcontrib><creatorcontrib>KAWAMOTO, Isao</creatorcontrib><creatorcontrib>IDE, Junya</creatorcontrib><creatorcontrib>NAKAO, Hideo</creatorcontrib><title>Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.</description><subject>Administration, Oral</subject><subject>Buffers</subject><subject>cefpodoxime proxetil</subject><subject>cephalosporin</subject><subject>Cephalosporins - administration & dosage</subject><subject>Cephalosporins - chemical synthesis</subject><subject>Cephalosporins - pharmacokinetics</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>CS-807</subject><subject>Drug Stability</subject><subject>Esters</subject><subject>Exact sciences and technology</subject><subject>isomerization</subject><subject>kinetics</subject><subject>Kinetics and mechanisms</subject><subject>Organic chemistry</subject><subject>Pentanoic Acids - administration & dosage</subject><subject>Pentanoic Acids - chemical synthesis</subject><subject>Pentanoic Acids - pharmacokinetics</subject><subject>Phosphates</subject><subject>prodrug</subject><subject>Reactivity and mechanisms</subject><subject>stability</subject><subject>Δ2 cephalosporin</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM-L1DAcxYMo6-zqybOQg3iR1vxo08bb7rjqwMIujJ5LmiY2S9rUJF3szT99U6aMl3wh7_PegwfAO4xyTIr6s5zanFY5oYy_ADtMiyorCaEvwQ4hxLP0T1-DyxAeESIlqugFuCAMlaziO_DvGOfOqADdCO-9sHaB1zKaJwX3auqFdWFy3ozwNkTlQw4Phxx-gfteDUYKC49RtMaauECn4YN5SobFur_LoGK_2M0Fk_-hT0m9iArezForD4_OztG48Q14pYUN6u12r8Cvb7c_9z-yu_vvh_31XSYLTnlWdTUhLep0q0XJ2k50NcOCEN0JVmBEukLSUpe40LjgkpG67YhsOZO1UoSUmF6Bj6fcybs_swqxGUyQyloxKjeHpuIFpoSgBH46gdK7ELzSzeTNIPzSYNSsezdp74ZWzbp3ot9vsXM7qO7MbgMn_cOmi5AG016M0oQzxipSccYS9vWEPYYofquzLnw00qq1EvOyXmv56Vnb_8u98I0a6TM_gqHE</recordid><startdate>1989</startdate><enddate>1989</enddate><creator>MIYAUCHI, Masao</creator><creator>SASAHARA, Kunihiro</creator><creator>FUJIMOTO, Koichi</creator><creator>KAWAMOTO, Isao</creator><creator>IDE, Junya</creator><creator>NAKAO, Hideo</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1989</creationdate><title>Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution</title><author>MIYAUCHI, Masao ; SASAHARA, Kunihiro ; FUJIMOTO, Koichi ; KAWAMOTO, Isao ; IDE, Junya ; NAKAO, Hideo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4939-7d822b0dfbfa56bdad861a22fda64102d4c35f514f149c628bd2cb96c8ee22513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Administration, Oral</topic><topic>Buffers</topic><topic>cefpodoxime proxetil</topic><topic>cephalosporin</topic><topic>Cephalosporins - administration & dosage</topic><topic>Cephalosporins - chemical synthesis</topic><topic>Cephalosporins - pharmacokinetics</topic><topic>Chemical Phenomena</topic><topic>Chemistry</topic><topic>CS-807</topic><topic>Drug Stability</topic><topic>Esters</topic><topic>Exact sciences and technology</topic><topic>isomerization</topic><topic>kinetics</topic><topic>Kinetics and mechanisms</topic><topic>Organic chemistry</topic><topic>Pentanoic Acids - administration & dosage</topic><topic>Pentanoic Acids - chemical synthesis</topic><topic>Pentanoic Acids - pharmacokinetics</topic><topic>Phosphates</topic><topic>prodrug</topic><topic>Reactivity and mechanisms</topic><topic>stability</topic><topic>Δ2 cephalosporin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MIYAUCHI, Masao</creatorcontrib><creatorcontrib>SASAHARA, Kunihiro</creatorcontrib><creatorcontrib>FUJIMOTO, Koichi</creatorcontrib><creatorcontrib>KAWAMOTO, Isao</creatorcontrib><creatorcontrib>IDE, Junya</creatorcontrib><creatorcontrib>NAKAO, Hideo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MIYAUCHI, Masao</au><au>SASAHARA, Kunihiro</au><au>FUJIMOTO, Koichi</au><au>KAWAMOTO, Isao</au><au>IDE, Junya</au><au>NAKAO, Hideo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1989</date><risdate>1989</risdate><volume>37</volume><issue>9</issue><spage>2369</spage><epage>2374</epage><pages>2369-2374</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><abstract>The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>2605679</pmid><doi>10.1248/cpb.37.2369</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | J-STAGE Free; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Administration, Oral Buffers cefpodoxime proxetil cephalosporin Cephalosporins - administration & dosage Cephalosporins - chemical synthesis Cephalosporins - pharmacokinetics Chemical Phenomena Chemistry CS-807 Drug Stability Esters Exact sciences and technology isomerization kinetics Kinetics and mechanisms Organic chemistry Pentanoic Acids - administration & dosage Pentanoic Acids - chemical synthesis Pentanoic Acids - pharmacokinetics Phosphates prodrug Reactivity and mechanisms stability Δ2 cephalosporin |
| title | Studies on Orally Active Cephalosporin Esters. II. : Chemical Stability of Pivaloyloxymethyl Esters in Phosphate Buffer Solution |
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