Population pharmacokinetics of marbofloxacin in horses: preliminary analysis
Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated th...
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| Veröffentlicht in: | Journal of veterinary pharmacology and therapeutics 2004-10, Vol.27 (5), p.283-288 |
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| creator | Peyrou, M Doucet, M.Y Vrins, A Concordet, D Schneider, M Bousquet-Melou, A |
| description | Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microgram/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC90 of Enterobacteriacae (0.027 microgram/mL). |
| doi_str_mv | 10.1111/j.1365-2885.2004.00591.x |
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Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microgram/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC90 of Enterobacteriacae (0.027 microgram/mL).</description><identifier>ISSN: 0140-7783</identifier><identifier>EISSN: 1365-2885</identifier><identifier>DOI: 10.1111/j.1365-2885.2004.00591.x</identifier><identifier>PMID: 15500564</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; Anti-Infective Agents ; Anti-Infective Agents - administration & dosage ; Anti-Infective Agents - blood ; Anti-Infective Agents - pharmacokinetics ; antibacterial properties ; antimicrobial agents ; Area Under Curve ; DNA Topoisomerases, Type II ; drug evaluation ; Enzyme Inhibitors ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - blood ; Enzyme Inhibitors - pharmacokinetics ; Female ; Fluoroquinolones ; Fluoroquinolones - administration & dosage ; Fluoroquinolones - blood ; Fluoroquinolones - pharmacokinetics ; Gastritis ; Gastritis - drug therapy ; Gastritis - veterinary ; Horse Diseases ; Horse Diseases - drug therapy ; Horse Diseases - metabolism ; Horses ; Horses - metabolism ; Injections, Intramuscular ; interindividual variability ; Life Sciences ; Male ; Mastitis ; Mastitis - drug therapy ; Mastitis - veterinary ; mixed effects models ; Pharmaceutical sciences ; pharmacokinetics ; Pharmacology ; Quinolones ; Quinolones - administration & dosage ; Quinolones - blood ; Quinolones - pharmacokinetics ; Regression Analysis ; Respiratory Tract Infections ; Respiratory Tract Infections - drug therapy ; Respiratory Tract Infections - veterinary ; Topoisomerase II Inhibitors ; veterinary drugs</subject><ispartof>Journal of veterinary pharmacology and therapeutics, 2004-10, Vol.27 (5), p.283-288</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4601-d34b984ea9a99246352933de8a293cebb9c998777d7c4ea2c164eeb11c308ac13</citedby><cites>FETCH-LOGICAL-c4601-d34b984ea9a99246352933de8a293cebb9c998777d7c4ea2c164eeb11c308ac13</cites><orcidid>0000-0003-3916-577X ; 0000-0002-7661-4311</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2885.2004.00591.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2885.2004.00591.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15500564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00517574$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Peyrou, M</creatorcontrib><creatorcontrib>Doucet, M.Y</creatorcontrib><creatorcontrib>Vrins, A</creatorcontrib><creatorcontrib>Concordet, D</creatorcontrib><creatorcontrib>Schneider, M</creatorcontrib><creatorcontrib>Bousquet-Melou, A</creatorcontrib><title>Population pharmacokinetics of marbofloxacin in horses: preliminary analysis</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J Vet Pharmacol Ther</addtitle><description>Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microgram/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC90 of Enterobacteriacae (0.027 microgram/mL).</description><subject>Animals</subject><subject>Anti-Infective Agents</subject><subject>Anti-Infective Agents - administration & dosage</subject><subject>Anti-Infective Agents - blood</subject><subject>Anti-Infective Agents - pharmacokinetics</subject><subject>antibacterial properties</subject><subject>antimicrobial agents</subject><subject>Area Under Curve</subject><subject>DNA Topoisomerases, Type II</subject><subject>drug evaluation</subject><subject>Enzyme Inhibitors</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Enzyme Inhibitors - blood</subject><subject>Enzyme Inhibitors - pharmacokinetics</subject><subject>Female</subject><subject>Fluoroquinolones</subject><subject>Fluoroquinolones - administration & dosage</subject><subject>Fluoroquinolones - blood</subject><subject>Fluoroquinolones - pharmacokinetics</subject><subject>Gastritis</subject><subject>Gastritis - drug therapy</subject><subject>Gastritis - veterinary</subject><subject>Horse Diseases</subject><subject>Horse Diseases - drug therapy</subject><subject>Horse Diseases - metabolism</subject><subject>Horses</subject><subject>Horses - metabolism</subject><subject>Injections, Intramuscular</subject><subject>interindividual variability</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mastitis</subject><subject>Mastitis - drug therapy</subject><subject>Mastitis - veterinary</subject><subject>mixed effects models</subject><subject>Pharmaceutical sciences</subject><subject>pharmacokinetics</subject><subject>Pharmacology</subject><subject>Quinolones</subject><subject>Quinolones - administration & dosage</subject><subject>Quinolones - blood</subject><subject>Quinolones - pharmacokinetics</subject><subject>Regression Analysis</subject><subject>Respiratory Tract Infections</subject><subject>Respiratory Tract Infections - drug therapy</subject><subject>Respiratory Tract Infections - veterinary</subject><subject>Topoisomerase II Inhibitors</subject><subject>veterinary drugs</subject><issn>0140-7783</issn><issn>1365-2885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkNFu0zAUhi0EYt3gFSBXSFwk2LETx4ibaUDLVI1JbHB5dOI61F0SB7sd7dvjkKrcYlmyZX__8fFHSMJoxuJ4t8kYL4s0r6oiyykVGaWFYtn-CZmdLp6SGWWCplJW_Iych7ChlPKKsefkjBVFTJRiRpa3bti1uLWuT4Y1-g61e7C92VodEtckHfraNa3bo7Z9Eufa-WDC-2TwprWd7dEfEuyxPQQbXpBnDbbBvDyuF-T-86e7q0W6_Dr_cnW5TLUoKUtXXNSqEgYVKpWLkhe54nxlKoyrNnWttFKVlHIldaRyzUphTM2Y5rRCzfgFeTvVXWMLg7exyQM4tLC4XMJ4Fj_HZCHF48i-mdjBu187E7bQ2aBN22Jv3C5AKaM_VeYRrCZQexeCN82pMqMwWocNjHJhlAujdfhrHfYx-ur4xq7uzOpf8Kg5Ah8m4LdtzeG_C8P199u4ifF0ituwNftTHP1DbJ_LAn7czOFaflzMbxZ3oCL_euIbdIA_vQ1w_y2njFOqYiAX_A9KHqh5</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Peyrou, M</creator><creator>Doucet, M.Y</creator><creator>Vrins, A</creator><creator>Concordet, D</creator><creator>Schneider, M</creator><creator>Bousquet-Melou, A</creator><general>Blackwell Science Ltd</general><general>Wiley-Blackwell</general><scope>FBQ</scope><scope>BSCLL</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><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-3916-577X</orcidid><orcidid>https://orcid.org/0000-0002-7661-4311</orcidid></search><sort><creationdate>200410</creationdate><title>Population pharmacokinetics of marbofloxacin in horses: preliminary analysis</title><author>Peyrou, M ; Doucet, M.Y ; Vrins, A ; Concordet, D ; Schneider, M ; Bousquet-Melou, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4601-d34b984ea9a99246352933de8a293cebb9c998777d7c4ea2c164eeb11c308ac13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Anti-Infective Agents</topic><topic>Anti-Infective Agents - administration & dosage</topic><topic>Anti-Infective Agents - blood</topic><topic>Anti-Infective Agents - pharmacokinetics</topic><topic>antibacterial properties</topic><topic>antimicrobial agents</topic><topic>Area Under Curve</topic><topic>DNA Topoisomerases, Type II</topic><topic>drug evaluation</topic><topic>Enzyme Inhibitors</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Enzyme Inhibitors - blood</topic><topic>Enzyme Inhibitors - pharmacokinetics</topic><topic>Female</topic><topic>Fluoroquinolones</topic><topic>Fluoroquinolones - administration & dosage</topic><topic>Fluoroquinolones - blood</topic><topic>Fluoroquinolones - pharmacokinetics</topic><topic>Gastritis</topic><topic>Gastritis - drug therapy</topic><topic>Gastritis - veterinary</topic><topic>Horse Diseases</topic><topic>Horse Diseases - drug therapy</topic><topic>Horse Diseases - metabolism</topic><topic>Horses</topic><topic>Horses - metabolism</topic><topic>Injections, Intramuscular</topic><topic>interindividual variability</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mastitis</topic><topic>Mastitis - drug therapy</topic><topic>Mastitis - veterinary</topic><topic>mixed effects models</topic><topic>Pharmaceutical sciences</topic><topic>pharmacokinetics</topic><topic>Pharmacology</topic><topic>Quinolones</topic><topic>Quinolones - administration & dosage</topic><topic>Quinolones - blood</topic><topic>Quinolones - pharmacokinetics</topic><topic>Regression Analysis</topic><topic>Respiratory Tract Infections</topic><topic>Respiratory Tract Infections - drug therapy</topic><topic>Respiratory Tract Infections - veterinary</topic><topic>Topoisomerase II Inhibitors</topic><topic>veterinary drugs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peyrou, M</creatorcontrib><creatorcontrib>Doucet, M.Y</creatorcontrib><creatorcontrib>Vrins, A</creatorcontrib><creatorcontrib>Concordet, D</creatorcontrib><creatorcontrib>Schneider, M</creatorcontrib><creatorcontrib>Bousquet-Melou, A</creatorcontrib><collection>AGRIS</collection><collection>Istex</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peyrou, M</au><au>Doucet, M.Y</au><au>Vrins, A</au><au>Concordet, D</au><au>Schneider, M</au><au>Bousquet-Melou, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population pharmacokinetics of marbofloxacin in horses: preliminary analysis</atitle><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle><addtitle>J Vet Pharmacol Ther</addtitle><date>2004-10</date><risdate>2004</risdate><volume>27</volume><issue>5</issue><spage>283</spage><epage>288</epage><pages>283-288</pages><issn>0140-7783</issn><eissn>1365-2885</eissn><abstract>Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microgram/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC90 of Enterobacteriacae (0.027 microgram/mL).</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15500564</pmid><doi>10.1111/j.1365-2885.2004.00591.x</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-3916-577X</orcidid><orcidid>https://orcid.org/0000-0002-7661-4311</orcidid></addata></record> |
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| subjects | Animals Anti-Infective Agents Anti-Infective Agents - administration & dosage Anti-Infective Agents - blood Anti-Infective Agents - pharmacokinetics antibacterial properties antimicrobial agents Area Under Curve DNA Topoisomerases, Type II drug evaluation Enzyme Inhibitors Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - blood Enzyme Inhibitors - pharmacokinetics Female Fluoroquinolones Fluoroquinolones - administration & dosage Fluoroquinolones - blood Fluoroquinolones - pharmacokinetics Gastritis Gastritis - drug therapy Gastritis - veterinary Horse Diseases Horse Diseases - drug therapy Horse Diseases - metabolism Horses Horses - metabolism Injections, Intramuscular interindividual variability Life Sciences Male Mastitis Mastitis - drug therapy Mastitis - veterinary mixed effects models Pharmaceutical sciences pharmacokinetics Pharmacology Quinolones Quinolones - administration & dosage Quinolones - blood Quinolones - pharmacokinetics Regression Analysis Respiratory Tract Infections Respiratory Tract Infections - drug therapy Respiratory Tract Infections - veterinary Topoisomerase II Inhibitors veterinary drugs |
| title | Population pharmacokinetics of marbofloxacin in horses: preliminary analysis |
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