Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens
Purpose This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. Methods Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dat...
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| Veröffentlicht in: | European journal of clinical pharmacology 2021-11, Vol.77 (11), p.1687-1695 |
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| creator | Hirt, D. Oualha, M. Pasquiers, B. Blanot, S. Rubinstazjn, R. Glorion, C. Messaoudi, S. El Drummond, D. Lopez, V. Toubiana, J. Béranger, A. Boujaafar, Sana Zheng, Yi Capito, Carmen Winter, S. Léger, P. L. Berthaud, R. Gana, Inès Foissac, F. Tréluyer, J. M. Bouazza, N. Benaboud, S. |
| description | Purpose
This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.
Methods
Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC
0-24 h
/MIC ratio ≥ 125.
Results
A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.
Conclusion
The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC
0-24 h
to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m
2
) in children |
| doi_str_mv | 10.1007/s00228-021-03174-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2583693739</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2583693739</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-391e1824541df72fbeb2c084a586c750b1acdc891742e2e71350e47f8e488343</originalsourceid><addsrcrecordid>eNp9kMFu1DAQhi1ERbctL8ABWeKcMmM7sXNEFQWkSvTQu-V1JluXxA52gqBPj2EL3DiN5Pnmn_HH2CuESwTQbwuAEKYBgQ1I1KrBZ2yHSooGQeFztoP63HS9hlN2VsoDALY9yBfsVCrsoOv6HQu3adkmt4YU-XLv8ux8-hIircEXnkYe4prdN4ppK9zFgafsJu7DktM4pe_Oh1gR7u_DNGSKfE08LWuYwyPxIZUQDzzTIcwUywU7Gd1U6OVTPWd31-_vrj42N58_fLp6d9N4qdu1kT0SGqFahcOoxbinvfBglGtN53ULe3R-8Kav_xUkSKNsgZQeDSljpJLn7M0xtp74daOy2oe05Vg3WtEa2fVSy75S4kj5nErJNNolh9nlHxbB_pJrj3JtlWt_y7VYh14_RW_7mYa_I39sVkAegVJb8UD53-7_xP4Eza2F9w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2583693739</pqid></control><display><type>article</type><title>Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Hirt, D. ; Oualha, M. ; Pasquiers, B. ; Blanot, S. ; Rubinstazjn, R. ; Glorion, C. ; Messaoudi, S. El ; Drummond, D. ; Lopez, V. ; Toubiana, J. ; Béranger, A. ; Boujaafar, Sana ; Zheng, Yi ; Capito, Carmen ; Winter, S. ; Léger, P. L. ; Berthaud, R. ; Gana, Inès ; Foissac, F. ; Tréluyer, J. M. ; Bouazza, N. ; Benaboud, S.</creator><creatorcontrib>Hirt, D. ; Oualha, M. ; Pasquiers, B. ; Blanot, S. ; Rubinstazjn, R. ; Glorion, C. ; Messaoudi, S. El ; Drummond, D. ; Lopez, V. ; Toubiana, J. ; Béranger, A. ; Boujaafar, Sana ; Zheng, Yi ; Capito, Carmen ; Winter, S. ; Léger, P. L. ; Berthaud, R. ; Gana, Inès ; Foissac, F. ; Tréluyer, J. M. ; Bouazza, N. ; Benaboud, S.</creatorcontrib><description>Purpose
This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.
Methods
Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC
0-24 h
/MIC ratio ≥ 125.
Results
A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.
Conclusion
The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC
0-24 h
to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m
2
) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-021-03174-1</identifier><identifier>PMID: 34160669</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Administration, Intravenous ; Adolescent ; Age Factors ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibiotics ; Area Under Curve ; Bacteremia - drug therapy ; Bacteria ; Biomedical and Life Sciences ; Biomedicine ; Body Height ; Body Weight ; Child ; Child, Preschool ; Children ; Ciprofloxacin ; Ciprofloxacin - administration & dosage ; Ciprofloxacin - pharmacokinetics ; Creatinine - blood ; Dosage ; Dose-Response Relationship, Drug ; Epidermal growth factor receptors ; Female ; Glomerular Filtration Rate ; Humans ; Infant ; Infant, Newborn ; Intravenous administration ; Male ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Models, Biological ; Monte Carlo Method ; Pharmacokinetics ; Pharmacokinetics and Disposition ; Pharmacology/Toxicology ; Prospective Studies ; Sex Factors ; Therapeutic drug monitoring</subject><ispartof>European journal of clinical pharmacology, 2021-11, Vol.77 (11), p.1687-1695</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-391e1824541df72fbeb2c084a586c750b1acdc891742e2e71350e47f8e488343</citedby><cites>FETCH-LOGICAL-c375t-391e1824541df72fbeb2c084a586c750b1acdc891742e2e71350e47f8e488343</cites><orcidid>0000-0002-9898-2609</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00228-021-03174-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-021-03174-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34160669$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirt, D.</creatorcontrib><creatorcontrib>Oualha, M.</creatorcontrib><creatorcontrib>Pasquiers, B.</creatorcontrib><creatorcontrib>Blanot, S.</creatorcontrib><creatorcontrib>Rubinstazjn, R.</creatorcontrib><creatorcontrib>Glorion, C.</creatorcontrib><creatorcontrib>Messaoudi, S. El</creatorcontrib><creatorcontrib>Drummond, D.</creatorcontrib><creatorcontrib>Lopez, V.</creatorcontrib><creatorcontrib>Toubiana, J.</creatorcontrib><creatorcontrib>Béranger, A.</creatorcontrib><creatorcontrib>Boujaafar, Sana</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Capito, Carmen</creatorcontrib><creatorcontrib>Winter, S.</creatorcontrib><creatorcontrib>Léger, P. L.</creatorcontrib><creatorcontrib>Berthaud, R.</creatorcontrib><creatorcontrib>Gana, Inès</creatorcontrib><creatorcontrib>Foissac, F.</creatorcontrib><creatorcontrib>Tréluyer, J. M.</creatorcontrib><creatorcontrib>Bouazza, N.</creatorcontrib><creatorcontrib>Benaboud, S.</creatorcontrib><title>Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Purpose
This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.
Methods
Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC
0-24 h
/MIC ratio ≥ 125.
Results
A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.
Conclusion
The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC
0-24 h
to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m
2
) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.</description><subject>Administration, Intravenous</subject><subject>Adolescent</subject><subject>Age Factors</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Antibiotics</subject><subject>Area Under Curve</subject><subject>Bacteremia - drug therapy</subject><subject>Bacteria</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body Height</subject><subject>Body Weight</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Ciprofloxacin</subject><subject>Ciprofloxacin - administration & dosage</subject><subject>Ciprofloxacin - pharmacokinetics</subject><subject>Creatinine - blood</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Glomerular Filtration Rate</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Microbial Sensitivity Tests</subject><subject>Minimum inhibitory concentration</subject><subject>Models, Biological</subject><subject>Monte Carlo Method</subject><subject>Pharmacokinetics</subject><subject>Pharmacokinetics and Disposition</subject><subject>Pharmacology/Toxicology</subject><subject>Prospective Studies</subject><subject>Sex Factors</subject><subject>Therapeutic drug monitoring</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kMFu1DAQhi1ERbctL8ABWeKcMmM7sXNEFQWkSvTQu-V1JluXxA52gqBPj2EL3DiN5Pnmn_HH2CuESwTQbwuAEKYBgQ1I1KrBZ2yHSooGQeFztoP63HS9hlN2VsoDALY9yBfsVCrsoOv6HQu3adkmt4YU-XLv8ux8-hIircEXnkYe4prdN4ppK9zFgafsJu7DktM4pe_Oh1gR7u_DNGSKfE08LWuYwyPxIZUQDzzTIcwUywU7Gd1U6OVTPWd31-_vrj42N58_fLp6d9N4qdu1kT0SGqFahcOoxbinvfBglGtN53ULe3R-8Kav_xUkSKNsgZQeDSljpJLn7M0xtp74daOy2oe05Vg3WtEa2fVSy75S4kj5nErJNNolh9nlHxbB_pJrj3JtlWt_y7VYh14_RW_7mYa_I39sVkAegVJb8UD53-7_xP4Eza2F9w</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Hirt, D.</creator><creator>Oualha, M.</creator><creator>Pasquiers, B.</creator><creator>Blanot, S.</creator><creator>Rubinstazjn, R.</creator><creator>Glorion, C.</creator><creator>Messaoudi, S. El</creator><creator>Drummond, D.</creator><creator>Lopez, V.</creator><creator>Toubiana, J.</creator><creator>Béranger, A.</creator><creator>Boujaafar, Sana</creator><creator>Zheng, Yi</creator><creator>Capito, Carmen</creator><creator>Winter, S.</creator><creator>Léger, P. L.</creator><creator>Berthaud, R.</creator><creator>Gana, Inès</creator><creator>Foissac, F.</creator><creator>Tréluyer, J. M.</creator><creator>Bouazza, N.</creator><creator>Benaboud, S.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>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><orcidid>https://orcid.org/0000-0002-9898-2609</orcidid></search><sort><creationdate>20211101</creationdate><title>Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens</title><author>Hirt, D. ; Oualha, M. ; Pasquiers, B. ; Blanot, S. ; Rubinstazjn, R. ; Glorion, C. ; Messaoudi, S. El ; Drummond, D. ; Lopez, V. ; Toubiana, J. ; Béranger, A. ; Boujaafar, Sana ; Zheng, Yi ; Capito, Carmen ; Winter, S. ; Léger, P. L. ; Berthaud, R. ; Gana, Inès ; Foissac, F. ; Tréluyer, J. M. ; Bouazza, N. ; Benaboud, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-391e1824541df72fbeb2c084a586c750b1acdc891742e2e71350e47f8e488343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Administration, Intravenous</topic><topic>Adolescent</topic><topic>Age Factors</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - pharmacokinetics</topic><topic>Antibiotics</topic><topic>Area Under Curve</topic><topic>Bacteremia - drug therapy</topic><topic>Bacteria</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Body Height</topic><topic>Body Weight</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Ciprofloxacin</topic><topic>Ciprofloxacin - administration & dosage</topic><topic>Ciprofloxacin - pharmacokinetics</topic><topic>Creatinine - blood</topic><topic>Dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Glomerular Filtration Rate</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Intravenous administration</topic><topic>Male</topic><topic>Microbial Sensitivity Tests</topic><topic>Minimum inhibitory concentration</topic><topic>Models, Biological</topic><topic>Monte Carlo Method</topic><topic>Pharmacokinetics</topic><topic>Pharmacokinetics and Disposition</topic><topic>Pharmacology/Toxicology</topic><topic>Prospective Studies</topic><topic>Sex Factors</topic><topic>Therapeutic drug monitoring</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirt, D.</creatorcontrib><creatorcontrib>Oualha, M.</creatorcontrib><creatorcontrib>Pasquiers, B.</creatorcontrib><creatorcontrib>Blanot, S.</creatorcontrib><creatorcontrib>Rubinstazjn, R.</creatorcontrib><creatorcontrib>Glorion, C.</creatorcontrib><creatorcontrib>Messaoudi, S. El</creatorcontrib><creatorcontrib>Drummond, D.</creatorcontrib><creatorcontrib>Lopez, V.</creatorcontrib><creatorcontrib>Toubiana, J.</creatorcontrib><creatorcontrib>Béranger, A.</creatorcontrib><creatorcontrib>Boujaafar, Sana</creatorcontrib><creatorcontrib>Zheng, Yi</creatorcontrib><creatorcontrib>Capito, Carmen</creatorcontrib><creatorcontrib>Winter, S.</creatorcontrib><creatorcontrib>Léger, P. L.</creatorcontrib><creatorcontrib>Berthaud, R.</creatorcontrib><creatorcontrib>Gana, Inès</creatorcontrib><creatorcontrib>Foissac, F.</creatorcontrib><creatorcontrib>Tréluyer, J. M.</creatorcontrib><creatorcontrib>Bouazza, N.</creatorcontrib><creatorcontrib>Benaboud, S.</creatorcontrib><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><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirt, D.</au><au>Oualha, M.</au><au>Pasquiers, B.</au><au>Blanot, S.</au><au>Rubinstazjn, R.</au><au>Glorion, C.</au><au>Messaoudi, S. El</au><au>Drummond, D.</au><au>Lopez, V.</au><au>Toubiana, J.</au><au>Béranger, A.</au><au>Boujaafar, Sana</au><au>Zheng, Yi</au><au>Capito, Carmen</au><au>Winter, S.</au><au>Léger, P. L.</au><au>Berthaud, R.</au><au>Gana, Inès</au><au>Foissac, F.</au><au>Tréluyer, J. M.</au><au>Bouazza, N.</au><au>Benaboud, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>77</volume><issue>11</issue><spage>1687</spage><epage>1695</epage><pages>1687-1695</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Purpose
This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.
Methods
Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC
0-24 h
/MIC ratio ≥ 125.
Results
A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.
Conclusion
The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC
0-24 h
to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m
2
) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34160669</pmid><doi>10.1007/s00228-021-03174-1</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9898-2609</orcidid></addata></record> |
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| ispartof | European journal of clinical pharmacology, 2021-11, Vol.77 (11), p.1687-1695 |
| issn | 0031-6970 1432-1041 |
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| subjects | Administration, Intravenous Adolescent Age Factors Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Area Under Curve Bacteremia - drug therapy Bacteria Biomedical and Life Sciences Biomedicine Body Height Body Weight Child Child, Preschool Children Ciprofloxacin Ciprofloxacin - administration & dosage Ciprofloxacin - pharmacokinetics Creatinine - blood Dosage Dose-Response Relationship, Drug Epidermal growth factor receptors Female Glomerular Filtration Rate Humans Infant Infant, Newborn Intravenous administration Male Microbial Sensitivity Tests Minimum inhibitory concentration Models, Biological Monte Carlo Method Pharmacokinetics Pharmacokinetics and Disposition Pharmacology/Toxicology Prospective Studies Sex Factors Therapeutic drug monitoring |
| title | Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens |
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