Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate
Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161–174. Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections....
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| description | Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161–174.
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration–time curve (AUC) and elimination half‐life (t½el) values were 9.99 and 10.11 μg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan‐induced exudate, lipopolysaccharide‐induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 μg h/mL after intravenous and 8.84, 8.53 and 8.52 μg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 μg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 μg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration‐dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24‐h incubation, virtually all bacteria were killed ( |
| doi_str_mv | 10.1046/j.1365-2885.2002.00399.x |
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Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration–time curve (AUC) and elimination half‐life (t½el) values were 9.99 and 10.11 μg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan‐induced exudate, lipopolysaccharide‐induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 μg h/mL after intravenous and 8.84, 8.53 and 8.52 μg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 μg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 μg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration‐dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24‐h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan‐induced exudate and transudate) and 36 h (lipopolysaccharide‐induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.</description><identifier>ISSN: 0140-7783</identifier><identifier>EISSN: 1365-2885</identifier><identifier>DOI: 10.1046/j.1365-2885.2002.00399.x</identifier><identifier>PMID: 12081611</identifier><language>eng</language><publisher>Oxford UK: Blackwell Science Ltd</publisher><subject>Animals ; Anti-Infective Agents - administration & dosage ; Anti-Infective Agents - blood ; Anti-Infective Agents - pharmacokinetics ; Anti-Infective Agents - pharmacology ; Area Under Curve ; Carrageenan ; Cattle - metabolism ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Exudates and Transudates - metabolism ; Fluoroquinolones ; Injections, Intramuscular - veterinary ; Injections, Intravenous - veterinary ; Lipopolysaccharides ; Male ; Mannheimia haemolytica - drug effects ; Microbial Sensitivity Tests ; Quinolones - administration & dosage ; Quinolones - blood ; Quinolones - pharmacokinetics ; Quinolones - pharmacology ; Tissue Distribution</subject><ispartof>Journal of veterinary pharmacology and therapeutics, 2002-06, Vol.25 (3), p.161-174</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4689-dbb87483fed6af6288c7124fc785850e0fba88e894de59074388073b5d9973a63</citedby><cites>FETCH-LOGICAL-c4689-dbb87483fed6af6288c7124fc785850e0fba88e894de59074388073b5d9973a63</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.1365-2885.2002.00399.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2885.2002.00399.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12081611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ALIABADI, F. SHOJAEE</creatorcontrib><creatorcontrib>LEES, P.</creatorcontrib><title>Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J Vet Pharmacol Ther</addtitle><description>Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161–174.
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration–time curve (AUC) and elimination half‐life (t½el) values were 9.99 and 10.11 μg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan‐induced exudate, lipopolysaccharide‐induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 μg h/mL after intravenous and 8.84, 8.53 and 8.52 μg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 μg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 μg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration‐dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24‐h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan‐induced exudate and transudate) and 36 h (lipopolysaccharide‐induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.</description><subject>Animals</subject><subject>Anti-Infective Agents - administration & dosage</subject><subject>Anti-Infective Agents - blood</subject><subject>Anti-Infective Agents - pharmacokinetics</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Area Under Curve</subject><subject>Carrageenan</subject><subject>Cattle - metabolism</subject><subject>Cross-Over Studies</subject><subject>Dose-Response Relationship, Drug</subject><subject>Exudates and Transudates - metabolism</subject><subject>Fluoroquinolones</subject><subject>Injections, Intramuscular - veterinary</subject><subject>Injections, Intravenous - veterinary</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Mannheimia haemolytica - drug effects</subject><subject>Microbial Sensitivity Tests</subject><subject>Quinolones - administration & dosage</subject><subject>Quinolones - blood</subject><subject>Quinolones - pharmacokinetics</subject><subject>Quinolones - pharmacology</subject><subject>Tissue Distribution</subject><issn>0140-7783</issn><issn>1365-2885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkFtv1DAQhS0EokvhLyA_8URSO07iicQLW0G3sIJK3B4txxmDt7ksdqJm_329F4p448kezzlnPB8hlLOUs7y82KRclEWSARRpxliWMiaqKp0fkcVD4zFZMJ6zREoQZ-RZCBsWVcD5U3LGMwa85HxB7m5-ad9pM9y6HkdnAtV9Q7f_Pl78qZtdrztnqOtH_On16IaeDpZ22teDbYdZG9fHJjW6tTSgn7rXFOep0SMeckev-3Aon5MnVrcBX5zOc_Lt_buvl6tk_fnq-vLtOjF5CVXS1DXIHITFptS2jHsZybPcGgkFFAyZrTUAQpU3WFRM5gKASVEXTVVJoUtxTl4dc7d--D1hGFXngsG21T0OU1CSQyGF5FEIR6HxQwgerdp6FxfbKc7UHrraqD1btWer9tDVAbqao_XlacZUd9j8NZ4oR8Gbo-DOtbj772D14ftNvER7crS7MOL8YNf-VpXx74X68elKrZfL5erLx5XKxT249KHJ</recordid><startdate>200206</startdate><enddate>200206</enddate><creator>ALIABADI, F. SHOJAEE</creator><creator>LEES, P.</creator><general>Blackwell Science Ltd</general><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></search><sort><creationdate>200206</creationdate><title>Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate</title><author>ALIABADI, F. SHOJAEE ; LEES, P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4689-dbb87483fed6af6288c7124fc785850e0fba88e894de59074388073b5d9973a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Anti-Infective Agents - administration & dosage</topic><topic>Anti-Infective Agents - blood</topic><topic>Anti-Infective Agents - pharmacokinetics</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Area Under Curve</topic><topic>Carrageenan</topic><topic>Cattle - metabolism</topic><topic>Cross-Over Studies</topic><topic>Dose-Response Relationship, Drug</topic><topic>Exudates and Transudates - metabolism</topic><topic>Fluoroquinolones</topic><topic>Injections, Intramuscular - veterinary</topic><topic>Injections, Intravenous - veterinary</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Mannheimia haemolytica - drug effects</topic><topic>Microbial Sensitivity Tests</topic><topic>Quinolones - administration & dosage</topic><topic>Quinolones - blood</topic><topic>Quinolones - pharmacokinetics</topic><topic>Quinolones - pharmacology</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ALIABADI, F. SHOJAEE</creatorcontrib><creatorcontrib>LEES, P.</creatorcontrib><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><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ALIABADI, F. SHOJAEE</au><au>LEES, P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate</atitle><jtitle>Journal of veterinary pharmacology and therapeutics</jtitle><addtitle>J Vet Pharmacol Ther</addtitle><date>2002-06</date><risdate>2002</risdate><volume>25</volume><issue>3</issue><spage>161</spage><epage>174</epage><pages>161-174</pages><issn>0140-7783</issn><eissn>1365-2885</eissn><abstract>Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161–174.
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration–time curve (AUC) and elimination half‐life (t½el) values were 9.99 and 10.11 μg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan‐induced exudate, lipopolysaccharide‐induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 μg h/mL after intravenous and 8.84, 8.53 and 8.52 μg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 μg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 μg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration‐dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24‐h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan‐induced exudate and transudate) and 36 h (lipopolysaccharide‐induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.</abstract><cop>Oxford UK</cop><pub>Blackwell Science Ltd</pub><pmid>12081611</pmid><doi>10.1046/j.1365-2885.2002.00399.x</doi><tpages>14</tpages></addata></record> |
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| subjects | Animals Anti-Infective Agents - administration & dosage Anti-Infective Agents - blood Anti-Infective Agents - pharmacokinetics Anti-Infective Agents - pharmacology Area Under Curve Carrageenan Cattle - metabolism Cross-Over Studies Dose-Response Relationship, Drug Exudates and Transudates - metabolism Fluoroquinolones Injections, Intramuscular - veterinary Injections, Intravenous - veterinary Lipopolysaccharides Male Mannheimia haemolytica - drug effects Microbial Sensitivity Tests Quinolones - administration & dosage Quinolones - blood Quinolones - pharmacokinetics Quinolones - pharmacology Tissue Distribution |
| title | Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate |
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