In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion
Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) a...
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| creator | Yu, Yang Zhou, Yu-Feng Chen, Mei-Ren Li, Xiao Qiao, Gui-Lin Sun, Jian Liao, Xiao-Ping Liu, Ya-Hong |
| description | Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml. |
| doi_str_mv | 10.1371/journal.pone.0156273 |
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Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0156273</identifier><identifier>PMID: 27218674</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal lactation ; Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibacterial activity ; Antibacterial agents ; Antimicrobial agents ; Area Under Curve ; Bacteria ; Bioavailability ; Biology and Life Sciences ; Cattle ; Causes of ; Cephalosporins ; Cephalosporins - administration & dosage ; Cephalosporins - pharmacokinetics ; Complications and side effects ; Dairy industry ; Disease Models, Animal ; Dosage ; Dosage and administration ; Drug resistance ; Drug therapy ; Economic impact ; Female ; Glands ; Injections ; Laboratory animals ; Mastitis ; Mastitis - drug therapy ; Mastitis - microbiology ; Medicine and Health Sciences ; Mice ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Modelling ; Morbidity ; Pharmaceutical sciences ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology ; Research and Analysis Methods ; Risk assessment ; Staphylococcal Infections - drug therapy ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Staphylococcus infections ; Treatment Outcome ; Veterinary medicine</subject><ispartof>PloS one, 2016-05, Vol.11 (5), p.e0156273-e0156273</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c686t-317eab531faf2d75f7611e7523e3c369292eb215a3032d64d0ce716c2479f77d3</citedby><cites>FETCH-LOGICAL-c686t-317eab531faf2d75f7611e7523e3c369292eb215a3032d64d0ce716c2479f77d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878769/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878769/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27218674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Zhou, Yu-Feng</creatorcontrib><creatorcontrib>Chen, Mei-Ren</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Qiao, Gui-Lin</creatorcontrib><creatorcontrib>Sun, Jian</creatorcontrib><creatorcontrib>Liao, Xiao-Ping</creatorcontrib><creatorcontrib>Liu, Ya-Hong</creatorcontrib><title>In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml.</description><subject>Animal lactation</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Antibacterial activity</subject><subject>Antibacterial agents</subject><subject>Antimicrobial agents</subject><subject>Area Under Curve</subject><subject>Bacteria</subject><subject>Bioavailability</subject><subject>Biology and Life Sciences</subject><subject>Cattle</subject><subject>Causes of</subject><subject>Cephalosporins</subject><subject>Cephalosporins - administration & dosage</subject><subject>Cephalosporins - pharmacokinetics</subject><subject>Complications and side effects</subject><subject>Dairy industry</subject><subject>Disease Models, Animal</subject><subject>Dosage</subject><subject>Dosage and administration</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Economic impact</subject><subject>Female</subject><subject>Glands</subject><subject>Injections</subject><subject>Laboratory animals</subject><subject>Mastitis</subject><subject>Mastitis - drug therapy</subject><subject>Mastitis - microbiology</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Microbial Sensitivity Tests</subject><subject>Minimum inhibitory concentration</subject><subject>Modelling</subject><subject>Morbidity</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Research and Analysis Methods</subject><subject>Risk assessment</subject><subject>Staphylococcal Infections - drug therapy</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus infections</subject><subject>Treatment Outcome</subject><subject>Veterinary medicine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBEQkJw0c4fie3cTKqqAZU2DTHYreU4duvi2F3sjPWf8HNxaDu1CAlu_HH8-LXPa58sewnBGGIKT5e-75yw45V3agxgSRDFj7JjWGE0Igjgx3vjo-xZCEsASswIeZodIYogI7Q4zn7OXH5j7nz-eSG6Vkj_3TgVjQynu0CzdqJNgdzrfKr0bW-cb1VuXC5cfn6_Up1plYvC5pe-Dyq1jbIDfB3FarG2Xnop-5BP-k6l7lKEaKIJufbW-h_GzfOZi51oRduKbp0mug_Gu-fZEy1sUC-2_Un27cP51-mn0cXVx9l0cjGShJE4wpAqUZcYaqFRQ0tNCYSKlggrLDGpUIVUjWApMMCoIUUDpKKQSFTQSlPa4JPs9UZ3ZX3gW1MDh7QCFcKIsETMNkTjxZKvUrrpntwLw38HfDfnokuWWcUpkzgdVyNEYQFQVWsopJSskTUDTT1onW1P6-tWNVINqdsD0cMVZxZ87u94wSijpEoC77YCnb_tVYi8NUEqa4VTyX4OGWAUVxCW_0ZpBSkgFA_omz_QvxuxpeYi5Wqc9umKchDlk6LEuKxYCRL1_oCS3kV1H-eiD4HPrr_8P3t1c8i-3WMXSti4CN72MX2WcAgWG1B2PoRO6Qd7IeBD6eyS40Pp8G3ppG2v9p_mYdOuVvAv3egW0Q</recordid><startdate>20160524</startdate><enddate>20160524</enddate><creator>Yu, Yang</creator><creator>Zhou, Yu-Feng</creator><creator>Chen, Mei-Ren</creator><creator>Li, Xiao</creator><creator>Qiao, Gui-Lin</creator><creator>Sun, Jian</creator><creator>Liao, Xiao-Ping</creator><creator>Liu, Ya-Hong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160524</creationdate><title>In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion</title><author>Yu, Yang ; Zhou, Yu-Feng ; Chen, Mei-Ren ; Li, Xiao ; Qiao, Gui-Lin ; Sun, Jian ; Liao, Xiao-Ping ; Liu, Ya-Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c686t-317eab531faf2d75f7611e7523e3c369292eb215a3032d64d0ce716c2479f77d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animal lactation</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - pharmacokinetics</topic><topic>Antibacterial activity</topic><topic>Antibacterial agents</topic><topic>Antimicrobial agents</topic><topic>Area Under Curve</topic><topic>Bacteria</topic><topic>Bioavailability</topic><topic>Biology and Life Sciences</topic><topic>Cattle</topic><topic>Causes of</topic><topic>Cephalosporins</topic><topic>Cephalosporins - administration & dosage</topic><topic>Cephalosporins - pharmacokinetics</topic><topic>Complications and side effects</topic><topic>Dairy industry</topic><topic>Disease Models, Animal</topic><topic>Dosage</topic><topic>Dosage and administration</topic><topic>Drug resistance</topic><topic>Drug therapy</topic><topic>Economic impact</topic><topic>Female</topic><topic>Glands</topic><topic>Injections</topic><topic>Laboratory animals</topic><topic>Mastitis</topic><topic>Mastitis - drug therapy</topic><topic>Mastitis - microbiology</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Microbial Sensitivity Tests</topic><topic>Minimum inhibitory concentration</topic><topic>Modelling</topic><topic>Morbidity</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Research and Analysis Methods</topic><topic>Risk assessment</topic><topic>Staphylococcal Infections - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Yang</au><au>Zhou, Yu-Feng</au><au>Chen, Mei-Ren</au><au>Li, Xiao</au><au>Qiao, Gui-Lin</au><au>Sun, Jian</au><au>Liao, Xiao-Ping</au><au>Liu, Ya-Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-05-24</date><risdate>2016</risdate><volume>11</volume><issue>5</issue><spage>e0156273</spage><epage>e0156273</epage><pages>e0156273-e0156273</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27218674</pmid><doi>10.1371/journal.pone.0156273</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2016-05, Vol.11 (5), p.e0156273-e0156273 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1790923268 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal lactation Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibacterial activity Antibacterial agents Antimicrobial agents Area Under Curve Bacteria Bioavailability Biology and Life Sciences Cattle Causes of Cephalosporins Cephalosporins - administration & dosage Cephalosporins - pharmacokinetics Complications and side effects Dairy industry Disease Models, Animal Dosage Dosage and administration Drug resistance Drug therapy Economic impact Female Glands Injections Laboratory animals Mastitis Mastitis - drug therapy Mastitis - microbiology Medicine and Health Sciences Mice Microbial Sensitivity Tests Minimum inhibitory concentration Modelling Morbidity Pharmaceutical sciences Pharmacodynamics Pharmacokinetics Pharmacology Research and Analysis Methods Risk assessment Staphylococcal Infections - drug therapy Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus infections Treatment Outcome Veterinary medicine |
| title | In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T23%3A27%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20Vivo%20Pharmacokinetics/Pharmacodynamics%20of%20Cefquinome%20in%20an%20Experimental%20Mouse%20Model%20of%20Staphylococcus%20Aureus%20Mastitis%20following%20Intramammary%20Infusion&rft.jtitle=PloS%20one&rft.au=Yu,%20Yang&rft.date=2016-05-24&rft.volume=11&rft.issue=5&rft.spage=e0156273&rft.epage=e0156273&rft.pages=e0156273-e0156273&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0156273&rft_dat=%3Cgale_plos_%3EA453359850%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1790923268&rft_id=info:pmid/27218674&rft_galeid=A453359850&rft_doaj_id=oai_doaj_org_article_78c3eb2b22714029bf1accc8dcb80db8&rfr_iscdi=true |