Factors affecting solubility and penetration of clarithromycin through gastric mucus
Background: Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined. Aim: To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier prop...
Gespeichert in:
| Veröffentlicht in: | Alimentary pharmacology & therapeutics 1998-06, Vol.12 (6), p.569-576 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 576 |
|---|---|
| container_issue | 6 |
| container_start_page | 569 |
| container_title | Alimentary pharmacology & therapeutics |
| container_volume | 12 |
| creator | GRÜBEL, P CAVE, D. R |
| description | Background:
Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.
Aim:
To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.
Methods:
Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.
Results:
Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.
Conclusions:
The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus. |
| doi_str_mv | 10.1046/j.1365-2036.1998.00329.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80035834</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>80035834</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4429-7207ecd51f0e9e36460be44d7c73a7a5bafa35c3f39c6f6a8d7bd9a463360ea3</originalsourceid><addsrcrecordid>eNqNkMtqwzAQRUVpadPHJxS0KN3ZlSxbD-gmlL4g0C6yF2NZShT8SCWbNn9fuwlZdzUD98xcOAhhSlJKcv6wSSnjRZIRxlOqlEwJYZlKf07Q7BicohnJuEoySdkFuoxxQwjhgmTn6FxxISWVM7R8AdN3IWJwzpretyscu3oofe37HYa2wlvb2j5A77sWdw6bGoLv16Frdsa3eNqG1RqvIPbBG9wMZojX6MxBHe3NYV6NNc_Lp7dk8fH6_jRfJCbPM5WIjAhrqoI6YpVlPOektHleCSMYCChKcMAKwxxThjsOshJlpSDnjHFigV2h-_3bbei-Bht73fhobF1Da7shajlKKSTLR1DuQRO6GIN1eht8A2GnKdGTT73RkzY9adOTT_3nU_-Mp7eHjqFsbHU8PAgc87tDDtFA7QK0xscjljEqCkVG7HGPffva7v5dr-efy3Fhv_Tjkm4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80035834</pqid></control><display><type>article</type><title>Factors affecting solubility and penetration of clarithromycin through gastric mucus</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>IngentaConnect Free/Open Access Journals</source><creator>GRÜBEL, P ; CAVE, D. R</creator><creatorcontrib>GRÜBEL, P ; CAVE, D. R</creatorcontrib><description>Background:
Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.
Aim:
To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.
Methods:
Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.
Results:
Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.
Conclusions:
The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1046/j.1365-2036.1998.00329.x</identifier><identifier>PMID: 9678818</identifier><language>eng</language><publisher>Oxford UK: Blackwell Science Ltd</publisher><subject>Absorption ; Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - metabolism ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Biological and medical sciences ; Biological Assay ; Clarithromycin - administration & dosage ; Clarithromycin - chemistry ; Clarithromycin - metabolism ; Gastric Mucins - isolation & purification ; Gastric Mucins - metabolism ; Gastric Mucosa - metabolism ; Hydrogen-Ion Concentration ; Medical sciences ; Mucus - metabolism ; Permeability ; Pharmacology. Drug treatments ; Solubility ; Swine ; Viscosity</subject><ispartof>Alimentary pharmacology & therapeutics, 1998-06, Vol.12 (6), p.569-576</ispartof><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4429-7207ecd51f0e9e36460be44d7c73a7a5bafa35c3f39c6f6a8d7bd9a463360ea3</citedby><cites>FETCH-LOGICAL-c4429-7207ecd51f0e9e36460be44d7c73a7a5bafa35c3f39c6f6a8d7bd9a463360ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2036.1998.00329.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2036.1998.00329.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2317590$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9678818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GRÜBEL, P</creatorcontrib><creatorcontrib>CAVE, D. R</creatorcontrib><title>Factors affecting solubility and penetration of clarithromycin through gastric mucus</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Background:
Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.
Aim:
To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.
Methods:
Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.
Results:
Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.
Conclusions:
The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus.</description><subject>Absorption</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Biological Assay</subject><subject>Clarithromycin - administration & dosage</subject><subject>Clarithromycin - chemistry</subject><subject>Clarithromycin - metabolism</subject><subject>Gastric Mucins - isolation & purification</subject><subject>Gastric Mucins - metabolism</subject><subject>Gastric Mucosa - metabolism</subject><subject>Hydrogen-Ion Concentration</subject><subject>Medical sciences</subject><subject>Mucus - metabolism</subject><subject>Permeability</subject><subject>Pharmacology. Drug treatments</subject><subject>Solubility</subject><subject>Swine</subject><subject>Viscosity</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtqwzAQRUVpadPHJxS0KN3ZlSxbD-gmlL4g0C6yF2NZShT8SCWbNn9fuwlZdzUD98xcOAhhSlJKcv6wSSnjRZIRxlOqlEwJYZlKf07Q7BicohnJuEoySdkFuoxxQwjhgmTn6FxxISWVM7R8AdN3IWJwzpretyscu3oofe37HYa2wlvb2j5A77sWdw6bGoLv16Frdsa3eNqG1RqvIPbBG9wMZojX6MxBHe3NYV6NNc_Lp7dk8fH6_jRfJCbPM5WIjAhrqoI6YpVlPOektHleCSMYCChKcMAKwxxThjsOshJlpSDnjHFigV2h-_3bbei-Bht73fhobF1Da7shajlKKSTLR1DuQRO6GIN1eht8A2GnKdGTT73RkzY9adOTT_3nU_-Mp7eHjqFsbHU8PAgc87tDDtFA7QK0xscjljEqCkVG7HGPffva7v5dr-efy3Fhv_Tjkm4</recordid><startdate>199806</startdate><enddate>199806</enddate><creator>GRÜBEL, P</creator><creator>CAVE, D. R</creator><general>Blackwell Science Ltd</general><general>Blackwell</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>199806</creationdate><title>Factors affecting solubility and penetration of clarithromycin through gastric mucus</title><author>GRÜBEL, P ; CAVE, D. R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4429-7207ecd51f0e9e36460be44d7c73a7a5bafa35c3f39c6f6a8d7bd9a463360ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Absorption</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - metabolism</topic><topic>Antibacterial agents</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Biological Assay</topic><topic>Clarithromycin - administration & dosage</topic><topic>Clarithromycin - chemistry</topic><topic>Clarithromycin - metabolism</topic><topic>Gastric Mucins - isolation & purification</topic><topic>Gastric Mucins - metabolism</topic><topic>Gastric Mucosa - metabolism</topic><topic>Hydrogen-Ion Concentration</topic><topic>Medical sciences</topic><topic>Mucus - metabolism</topic><topic>Permeability</topic><topic>Pharmacology. Drug treatments</topic><topic>Solubility</topic><topic>Swine</topic><topic>Viscosity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GRÜBEL, P</creatorcontrib><creatorcontrib>CAVE, D. R</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>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GRÜBEL, P</au><au>CAVE, D. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Factors affecting solubility and penetration of clarithromycin through gastric mucus</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>1998-06</date><risdate>1998</risdate><volume>12</volume><issue>6</issue><spage>569</spage><epage>576</epage><pages>569-576</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Background:
Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.
Aim:
To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.
Methods:
Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.
Results:
Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.
Conclusions:
The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus.</abstract><cop>Oxford UK</cop><pub>Blackwell Science Ltd</pub><pmid>9678818</pmid><doi>10.1046/j.1365-2036.1998.00329.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0269-2813 |
| ispartof | Alimentary pharmacology & therapeutics, 1998-06, Vol.12 (6), p.569-576 |
| issn | 0269-2813 1365-2036 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80035834 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; IngentaConnect Free/Open Access Journals |
| subjects | Absorption Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - metabolism Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Biological and medical sciences Biological Assay Clarithromycin - administration & dosage Clarithromycin - chemistry Clarithromycin - metabolism Gastric Mucins - isolation & purification Gastric Mucins - metabolism Gastric Mucosa - metabolism Hydrogen-Ion Concentration Medical sciences Mucus - metabolism Permeability Pharmacology. Drug treatments Solubility Swine Viscosity |
| title | Factors affecting solubility and penetration of clarithromycin through gastric mucus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T12%3A43%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Factors%20affecting%20solubility%20and%20penetration%20of%20clarithromycin%20through%20gastric%20mucus&rft.jtitle=Alimentary%20pharmacology%20&%20therapeutics&rft.au=GR%C3%9CBEL,%20P&rft.date=1998-06&rft.volume=12&rft.issue=6&rft.spage=569&rft.epage=576&rft.pages=569-576&rft.issn=0269-2813&rft.eissn=1365-2036&rft_id=info:doi/10.1046/j.1365-2036.1998.00329.x&rft_dat=%3Cproquest_cross%3E80035834%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=80035834&rft_id=info:pmid/9678818&rfr_iscdi=true |