Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin
Aims To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin. Methods Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multipl...
Gespeichert in:
| Veröffentlicht in: | European journal of clinical pharmacology 2013-03, Vol.69 (3), p.439-448 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 448 |
|---|---|
| container_issue | 3 |
| container_start_page | 439 |
| container_title | European journal of clinical pharmacology |
| container_volume | 69 |
| creator | Quinney, Sara K. Malireddy, Srikar R. Vuppalanchi, Raj Hamman, Mitchell A. Chalasani, Naga Gorski, J. Christopher Hall, Stephen D. |
| description | Aims
To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin.
Methods
Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2–4, and on days 6–8 of the clarithromycin treatment. The formation of 1′-hydroxymidazolam in biopsy tissue and the serum 1′-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively.
Results
Intestinal CYP3A activity decreased by 64 % (
p
= 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (
p
= 0.005), while intestinal activity showed little further decline. The
CYP3A5
or
CYP3A4*1B
genotype were unable to account for inter-individual variability in CYP3A activity.
Conclusions
Following the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug–drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate. |
| doi_str_mv | 10.1007/s00228-012-1339-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3712509</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2891077291</sourcerecordid><originalsourceid>FETCH-LOGICAL-c566t-eb661ed7c5d7a2a3aec369e52c7b7cdb8f22c8720e5093ff6f1244352b3ecd73</originalsourceid><addsrcrecordid>eNp1kM1OwzAQhC0EoqXwAFxQJMQxsLaTOLkgoYo_UQmEeuFkOY7TukrtYrvQvj2JWgocONmr_XZ2dhA6xXCJAdiVByAkjwGTGFNaxKs91McJbStI8D7qA1AcZwWDHjryfgaA0wLoIeoRwhjDSd5HT68iqMjWkTVehe6jzVSXOmhrumqyDPGnaJpImCqaqoUIWkbDtxd6E5XrSDbC6TB1dr6W2hyjg1o0Xp1s3wEa392Ohw_x6Pn-cXgzimWaZSFWZZZhVTGZVkwQQYWSNCtUSiQrmazKvCZE5oyASqGgdZ3VmCQJTUlJlawYHaDrjexiWc5VJZUJTjR84fRcuDW3QvO_HaOnfGI_OGWYdJIDdL4VcPZ9qXzgM7t0prXMMckZTZOMQEvhDSWd9d6percBA-_i55v4eRs_7-Lnq3bm7Le13cR33i1wsQWEl6KpnTBS-x-OpaxgtLuRbDjftsxEuV8W_93-Ba0Ongs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1287354620</pqid></control><display><type>article</type><title>Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Quinney, Sara K. ; Malireddy, Srikar R. ; Vuppalanchi, Raj ; Hamman, Mitchell A. ; Chalasani, Naga ; Gorski, J. Christopher ; Hall, Stephen D.</creator><creatorcontrib>Quinney, Sara K. ; Malireddy, Srikar R. ; Vuppalanchi, Raj ; Hamman, Mitchell A. ; Chalasani, Naga ; Gorski, J. Christopher ; Hall, Stephen D.</creatorcontrib><description>Aims
To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin.
Methods
Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2–4, and on days 6–8 of the clarithromycin treatment. The formation of 1′-hydroxymidazolam in biopsy tissue and the serum 1′-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively.
Results
Intestinal CYP3A activity decreased by 64 % (
p
= 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (
p
= 0.005), while intestinal activity showed little further decline. The
CYP3A5
or
CYP3A4*1B
genotype were unable to account for inter-individual variability in CYP3A activity.
Conclusions
Following the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug–drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-012-1339-x</identifier><identifier>PMID: 22777148</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Administration, Oral ; Adult ; Analysis of Variance ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Biotransformation ; Clarithromycin - administration & dosage ; Cytochrome P-450 CYP3A - genetics ; Cytochrome P-450 CYP3A - metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Drug Administration Schedule ; Drug therapy ; Duodenum - drug effects ; Duodenum - enzymology ; Enzyme Inhibitors - administration & dosage ; Female ; Genotype ; Humans ; Hydroxylation ; Inhibitor drugs ; Liver - drug effects ; Liver - enzymology ; Male ; Medical sciences ; Midazolam - administration & dosage ; Midazolam - analogs & derivatives ; Midazolam - pharmacokinetics ; Middle Aged ; Pharmacokinetics and Disposition ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Phenotype ; Small intestine ; Substrate Specificity ; Young Adult</subject><ispartof>European journal of clinical pharmacology, 2013-03, Vol.69 (3), p.439-448</ispartof><rights>Springer-Verlag 2012</rights><rights>2014 INIST-CNRS</rights><rights>Springer-Verlag Berlin Heidelberg 2013</rights><rights>Springer-Verlag 2012 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-eb661ed7c5d7a2a3aec369e52c7b7cdb8f22c8720e5093ff6f1244352b3ecd73</citedby><cites>FETCH-LOGICAL-c566t-eb661ed7c5d7a2a3aec369e52c7b7cdb8f22c8720e5093ff6f1244352b3ecd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00228-012-1339-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-012-1339-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27579737$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22777148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quinney, Sara K.</creatorcontrib><creatorcontrib>Malireddy, Srikar R.</creatorcontrib><creatorcontrib>Vuppalanchi, Raj</creatorcontrib><creatorcontrib>Hamman, Mitchell A.</creatorcontrib><creatorcontrib>Chalasani, Naga</creatorcontrib><creatorcontrib>Gorski, J. Christopher</creatorcontrib><creatorcontrib>Hall, Stephen D.</creatorcontrib><title>Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Aims
To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin.
Methods
Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2–4, and on days 6–8 of the clarithromycin treatment. The formation of 1′-hydroxymidazolam in biopsy tissue and the serum 1′-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively.
Results
Intestinal CYP3A activity decreased by 64 % (
p
= 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (
p
= 0.005), while intestinal activity showed little further decline. The
CYP3A5
or
CYP3A4*1B
genotype were unable to account for inter-individual variability in CYP3A activity.
Conclusions
Following the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug–drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biopsy</subject><subject>Biotransformation</subject><subject>Clarithromycin - administration & dosage</subject><subject>Cytochrome P-450 CYP3A - genetics</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Cytochrome P-450 CYP3A Inhibitors</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Duodenum - drug effects</subject><subject>Duodenum - enzymology</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hydroxylation</subject><subject>Inhibitor drugs</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Midazolam - administration & dosage</subject><subject>Midazolam - analogs & derivatives</subject><subject>Midazolam - pharmacokinetics</subject><subject>Middle Aged</subject><subject>Pharmacokinetics and Disposition</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotype</subject><subject>Small intestine</subject><subject>Substrate Specificity</subject><subject>Young Adult</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kM1OwzAQhC0EoqXwAFxQJMQxsLaTOLkgoYo_UQmEeuFkOY7TukrtYrvQvj2JWgocONmr_XZ2dhA6xXCJAdiVByAkjwGTGFNaxKs91McJbStI8D7qA1AcZwWDHjryfgaA0wLoIeoRwhjDSd5HT68iqMjWkTVehe6jzVSXOmhrumqyDPGnaJpImCqaqoUIWkbDtxd6E5XrSDbC6TB1dr6W2hyjg1o0Xp1s3wEa392Ohw_x6Pn-cXgzimWaZSFWZZZhVTGZVkwQQYWSNCtUSiQrmazKvCZE5oyASqGgdZ3VmCQJTUlJlawYHaDrjexiWc5VJZUJTjR84fRcuDW3QvO_HaOnfGI_OGWYdJIDdL4VcPZ9qXzgM7t0prXMMckZTZOMQEvhDSWd9d6percBA-_i55v4eRs_7-Lnq3bm7Le13cR33i1wsQWEl6KpnTBS-x-OpaxgtLuRbDjftsxEuV8W_93-Ba0Ongs</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Quinney, Sara K.</creator><creator>Malireddy, Srikar R.</creator><creator>Vuppalanchi, Raj</creator><creator>Hamman, Mitchell A.</creator><creator>Chalasani, Naga</creator><creator>Gorski, J. Christopher</creator><creator>Hall, Stephen D.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20130301</creationdate><title>Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin</title><author>Quinney, Sara K. ; Malireddy, Srikar R. ; Vuppalanchi, Raj ; Hamman, Mitchell A. ; Chalasani, Naga ; Gorski, J. Christopher ; Hall, Stephen D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-eb661ed7c5d7a2a3aec369e52c7b7cdb8f22c8720e5093ff6f1244352b3ecd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biopsy</topic><topic>Biotransformation</topic><topic>Clarithromycin - administration & dosage</topic><topic>Cytochrome P-450 CYP3A - genetics</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>Cytochrome P-450 CYP3A Inhibitors</topic><topic>Drug Administration Schedule</topic><topic>Drug therapy</topic><topic>Duodenum - drug effects</topic><topic>Duodenum - enzymology</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hydroxylation</topic><topic>Inhibitor drugs</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Midazolam - administration & dosage</topic><topic>Midazolam - analogs & derivatives</topic><topic>Midazolam - pharmacokinetics</topic><topic>Middle Aged</topic><topic>Pharmacokinetics and Disposition</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotype</topic><topic>Small intestine</topic><topic>Substrate Specificity</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quinney, Sara K.</creatorcontrib><creatorcontrib>Malireddy, Srikar R.</creatorcontrib><creatorcontrib>Vuppalanchi, Raj</creatorcontrib><creatorcontrib>Hamman, Mitchell A.</creatorcontrib><creatorcontrib>Chalasani, Naga</creatorcontrib><creatorcontrib>Gorski, J. Christopher</creatorcontrib><creatorcontrib>Hall, Stephen D.</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quinney, Sara K.</au><au>Malireddy, Srikar R.</au><au>Vuppalanchi, Raj</au><au>Hamman, Mitchell A.</au><au>Chalasani, Naga</au><au>Gorski, J. Christopher</au><au>Hall, Stephen D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>69</volume><issue>3</issue><spage>439</spage><epage>448</epage><pages>439-448</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Aims
To determine the extent and time-course of hepatic and intestinal cytochrome P450 3A (CYP3A) inactivation due to the mechanism-based inhibitor clarithromycin.
Methods
Intestinal and hepatic CYP3A inhibition was examined in 12 healthy volunteers following the administration of single and multiple doses of oral clarithromycin (500 mg). Intestinal biopsies were obtained under intravenous midazolam sedation at baseline and after the first dose, on days 2–4, and on days 6–8 of the clarithromycin treatment. The formation of 1′-hydroxymidazolam in biopsy tissue and the serum 1′-hydroxymidazolam:midazolam ratio were indicators of intestinal and hepatic CYP3A activity, respectively.
Results
Intestinal CYP3A activity decreased by 64 % (
p
= 0.0029) following the first dose of clarithromycin, but hepatic CYP3A activity did not significantly decrease. Repeated dosing of clarithromycin caused a significant decrease in hepatic CYP3A activity (
p
= 0.005), while intestinal activity showed little further decline. The
CYP3A5
or
CYP3A4*1B
genotype were unable to account for inter-individual variability in CYP3A activity.
Conclusions
Following the administration of clarithromycin, the onset of hepatic CYP3A inactivation is delayed compared to that of intestinal CYP3A. The time-course of drug–drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22777148</pmid><doi>10.1007/s00228-012-1339-x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-6970 |
| ispartof | European journal of clinical pharmacology, 2013-03, Vol.69 (3), p.439-448 |
| issn | 0031-6970 1432-1041 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3712509 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Administration, Oral Adult Analysis of Variance Biological and medical sciences Biomedical and Life Sciences Biomedicine Biopsy Biotransformation Clarithromycin - administration & dosage Cytochrome P-450 CYP3A - genetics Cytochrome P-450 CYP3A - metabolism Cytochrome P-450 CYP3A Inhibitors Drug Administration Schedule Drug therapy Duodenum - drug effects Duodenum - enzymology Enzyme Inhibitors - administration & dosage Female Genotype Humans Hydroxylation Inhibitor drugs Liver - drug effects Liver - enzymology Male Medical sciences Midazolam - administration & dosage Midazolam - analogs & derivatives Midazolam - pharmacokinetics Middle Aged Pharmacokinetics and Disposition Pharmacology. Drug treatments Pharmacology/Toxicology Phenotype Small intestine Substrate Specificity Young Adult |
| title | Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T10%3A22%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rate%20of%20onset%20of%20inhibition%20of%20gut-wall%20and%20hepatic%20CYP3A%20by%20clarithromycin&rft.jtitle=European%20journal%20of%20clinical%20pharmacology&rft.au=Quinney,%20Sara%20K.&rft.date=2013-03-01&rft.volume=69&rft.issue=3&rft.spage=439&rft.epage=448&rft.pages=439-448&rft.issn=0031-6970&rft.eissn=1432-1041&rft_id=info:doi/10.1007/s00228-012-1339-x&rft_dat=%3Cproquest_pubme%3E2891077291%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1287354620&rft_id=info:pmid/22777148&rfr_iscdi=true |