Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats

The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h...

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Veröffentlicht in:Research in veterinary science 2018-12, Vol.121, p.111-115
Hauptverfasser: Bhardwaj, Pallavi, Sidhu, Pritam K., Lonare, M.K., Kaur, Rajdeep, Dumka, V.K., Rampal, S.
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container_end_page 115
container_issue
container_start_page 111
container_title Research in veterinary science
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creator Bhardwaj, Pallavi
Sidhu, Pritam K.
Lonare, M.K.
Kaur, Rajdeep
Dumka, V.K.
Rampal, S.
description The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t1/2elm = 4.37 ± 0.18 h and ClB = 0.29 ± 0.01 following single administration were not significantly different from t1/2elm = 5.11 ± 0.22 h and ClB = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC0–24h/MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC90 = 0.12 μg/mL in goat species. •Pharmacokinetics of marbofloxacin was not altered following single and repeated IV administrations in goats.•The AUCs were 7.69 ± 0.26 µg/mL.h and 6.99 ± 0.17 µg/mL.h on 5th and 1st administration of marbofloxacin, respectively.•No drug accumulation (AI=1.1) following repeated IV administrations up to 5 days was observed in goats.•Marbofloxacin dosage of 2 mg/kg/24h was determined for treatment of E. coli (MIC ≤ 0.03 µg/mL) infections in goats.•A revised dosage of 6 mg/kg/24h is indicated to obtain clinical cure against P. multocida (MIC90 = 0.12 µg/mL).
doi_str_mv 10.1016/j.rvsc.2018.10.010
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Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t1/2elm = 4.37 ± 0.18 h and ClB = 0.29 ± 0.01 following single administration were not significantly different from t1/2elm = 5.11 ± 0.22 h and ClB = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC0–24h/MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. 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Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t1/2elm = 4.37 ± 0.18 h and ClB = 0.29 ± 0.01 following single administration were not significantly different from t1/2elm = 5.11 ± 0.22 h and ClB = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC0–24h/MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC90 = 0.12 μg/mL in goat species. •Pharmacokinetics of marbofloxacin was not altered following single and repeated IV administrations in goats.•The AUCs were 7.69 ± 0.26 µg/mL.h and 6.99 ± 0.17 µg/mL.h on 5th and 1st administration of marbofloxacin, respectively.•No drug accumulation (AI=1.1) following repeated IV administrations up to 5 days was observed in goats.•Marbofloxacin dosage of 2 mg/kg/24h was determined for treatment of E. coli (MIC ≤ 0.03 µg/mL) infections in goats.•A revised dosage of 6 mg/kg/24h is indicated to obtain clinical cure against P. multocida (MIC90 = 0.12 µg/mL).</description><subject>Accumulation</subject><subject>Administration, Intravenous - methods</subject><subject>Administration, Intravenous - veterinary</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Area Under Curve</subject><subject>Body weight</subject><subject>Caprinae</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid - veterinary</subject><subject>Dosage</subject><subject>Drug dosages</subject><subject>E coli</subject><subject>Escherichia coli - drug effects</subject><subject>Female</subject><subject>Fluoroquinolones - pharmacokinetics</subject><subject>Fluoroquinolones - pharmacology</subject><subject>Goat</subject><subject>Goats</subject><subject>Goats - metabolism</subject><subject>High performance liquid chromatography</subject><subject>Infections</subject><subject>Integration</subject><subject>Intravenous</subject><subject>Intravenous administration</subject><subject>Liquid chromatography</subject><subject>Marbofloxacin</subject><subject>Microbial Sensitivity Tests - veterinary</subject><subject>Minimum inhibitory concentration</subject><subject>Pasteurella multocida - drug effects</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>PK/PD integration</subject><subject>Repeated administration</subject><subject>Studies</subject><subject>Veterinary medicine</subject><issn>0034-5288</issn><issn>1532-2661</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuLFDEUhYMoTjv6B1xIgRs31eYm9UiBGxnGBwzoQtchj5s2bVXSJunG8debolsXLlxd7uU7h8M9hDwHugUKw-v9Np2y2TIKoh62FOgDsoGes5YNAzwkG0p51_ZMiCvyJOc9pbQDGB-TK0656KCDDfn1-ZtKizLxuw9YvGkPl93eB7V40_hQcJdU8TE00TWLSjq6Of5UxodGuYKpyT7sZmxUsE3CA6qCdpUldcIQj7lRdvHB53JxqbpdVCU_JY-cmjM-u8xr8vXd7ZebD-3dp_cfb97etaaGLK0bJ8SRa4ZKYzcOCEoP3cRtLyh2otdOaO4o15MG0E6PrrfDNFQVHSbFBL8mr86-hxR_HDEXufhscJ5VwBpPMmBTz8deTBV9-Q-6j8cUarpKcegFg66rFDtTJsWcEzp5SL4-5l4ClWszci_XZuTazHqrzVTRi4v1US9o_0r-VFGBN2cA6y9OHpPMxmMwaH1CU6SN_n_-vwGXtqJs</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Bhardwaj, Pallavi</creator><creator>Sidhu, Pritam K.</creator><creator>Lonare, M.K.</creator><creator>Kaur, Rajdeep</creator><creator>Dumka, V.K.</creator><creator>Rampal, S.</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201812</creationdate><title>Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats</title><author>Bhardwaj, Pallavi ; 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Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t1/2elm = 4.37 ± 0.18 h and ClB = 0.29 ± 0.01 following single administration were not significantly different from t1/2elm = 5.11 ± 0.22 h and ClB = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC0–24h/MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC90 = 0.12 μg/mL in goat species. •Pharmacokinetics of marbofloxacin was not altered following single and repeated IV administrations in goats.•The AUCs were 7.69 ± 0.26 µg/mL.h and 6.99 ± 0.17 µg/mL.h on 5th and 1st administration of marbofloxacin, respectively.•No drug accumulation (AI=1.1) following repeated IV administrations up to 5 days was observed in goats.•Marbofloxacin dosage of 2 mg/kg/24h was determined for treatment of E. coli (MIC ≤ 0.03 µg/mL) infections in goats.•A revised dosage of 6 mg/kg/24h is indicated to obtain clinical cure against P. multocida (MIC90 = 0.12 µg/mL).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30384141</pmid><doi>10.1016/j.rvsc.2018.10.010</doi><tpages>5</tpages></addata></record>
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subjects Accumulation
Administration, Intravenous - methods
Administration, Intravenous - veterinary
Animals
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Antibiotics
Antimicrobial agents
Area Under Curve
Body weight
Caprinae
Chromatography
Chromatography, High Pressure Liquid - veterinary
Dosage
Drug dosages
E coli
Escherichia coli - drug effects
Female
Fluoroquinolones - pharmacokinetics
Fluoroquinolones - pharmacology
Goat
Goats
Goats - metabolism
High performance liquid chromatography
Infections
Integration
Intravenous
Intravenous administration
Liquid chromatography
Marbofloxacin
Microbial Sensitivity Tests - veterinary
Minimum inhibitory concentration
Pasteurella multocida - drug effects
Pharmacodynamics
Pharmacokinetics
Pharmacology
PK/PD integration
Repeated administration
Studies
Veterinary medicine
title Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats
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