Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)
Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-...
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creator | Lodise, Thomas P Van Wart, Scott Sund, Zoe M Bressler, Adam M Khan, Akram Makley, Amy T Hamad, Yasir Salata, Robert A Silveira, Fernanda P Sims, Matthew D Kabchi, Badih A Saad, Mohamed A Brown, Carrie Oler, Jr, Randolph E Fowler, Jr, Vance Wunderink, Richard G |
description | Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR)
Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [
AUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of
were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f
) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f
). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with
infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation. |
doi_str_mv | 10.1128/AAC.01809-20 |
format | Article |
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Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [
AUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of
were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f
) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f
). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with
infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.01809-20</identifier><identifier>PMID: 33168615</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Acinetobacter baumannii ; Adult ; Animals ; Anti-Bacterial Agents - therapeutic use ; Clinical Therapeutics ; Critical Illness ; Humans ; Microbial Sensitivity Tests ; Minocycline</subject><ispartof>Antimicrobial agents and chemotherapy, 2021-02, Vol.65 (3)</ispartof><rights>Copyright © 2021 American Society for Microbiology.</rights><rights>Copyright © 2021 American Society for Microbiology. 2021 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a3330-df9acdb22c0f049030fcf75c914fd0315dfbabe084d0c6eb47ac400608caaf7a3</citedby><cites>FETCH-LOGICAL-a3330-df9acdb22c0f049030fcf75c914fd0315dfbabe084d0c6eb47ac400608caaf7a3</cites><orcidid>0000-0002-4730-0655 ; 0000-0001-6616-7127</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092545/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092545/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33168615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lodise, Thomas P</creatorcontrib><creatorcontrib>Van Wart, Scott</creatorcontrib><creatorcontrib>Sund, Zoe M</creatorcontrib><creatorcontrib>Bressler, Adam M</creatorcontrib><creatorcontrib>Khan, Akram</creatorcontrib><creatorcontrib>Makley, Amy T</creatorcontrib><creatorcontrib>Hamad, Yasir</creatorcontrib><creatorcontrib>Salata, Robert A</creatorcontrib><creatorcontrib>Silveira, Fernanda P</creatorcontrib><creatorcontrib>Sims, Matthew D</creatorcontrib><creatorcontrib>Kabchi, Badih A</creatorcontrib><creatorcontrib>Saad, Mohamed A</creatorcontrib><creatorcontrib>Brown, Carrie</creatorcontrib><creatorcontrib>Oler, Jr, Randolph E</creatorcontrib><creatorcontrib>Fowler, Jr, Vance</creatorcontrib><creatorcontrib>Wunderink, Richard G</creatorcontrib><title>Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR)
Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [
AUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of
were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f
) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f
). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with
infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.</description><subject>Acinetobacter baumannii</subject><subject>Adult</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Clinical Therapeutics</subject><subject>Critical Illness</subject><subject>Humans</subject><subject>Microbial Sensitivity Tests</subject><subject>Minocycline</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UU1v1DAQtRCILoUbZ-QjlUgZ52uTC1IU8bHSLq1UytWa-KP14tgrJwHld_UP1mFpBQdOo5n3_N6MHyGvGZwzllbvm6Y9B1ZBnaTwhKwY1FVSFnX5lKwAyjLJK8hPyIth2EPsixqek5MsY2VVsmJF7i5vMfQo_A_j1GgERSfpw0zODvs4uwxeG2vcDfWa7ozzYhaxVVT7QDdur8RovIudtf7XQkN6FYtVEdTTsGDG0TaYaIDWznRjLW3kZMdhAXAxHCL5O704KJdssVOW7iJshHKjCvRqnORM3zbt9W7z9ewleabRDurVn3pKrj99_NZ-SbYXnzdts00wyzJIpK5RyC5NBWjIa8hAC70uRM1yLSFjhdRddIIqlyBK1eVrFHn8IqgEol5jdko-HHUPU9cruewS0PJDMD2GmXs0_F_EmVt-43_yGEZa5EUUeHcUEMEPQ1D68S0DvoTHY3j8d3g8hUg_O9Jx6FO-91Nw8bz_cd_8vduj8EOy2T0fjKW4</recordid><startdate>20210217</startdate><enddate>20210217</enddate><creator>Lodise, Thomas P</creator><creator>Van Wart, Scott</creator><creator>Sund, Zoe M</creator><creator>Bressler, Adam M</creator><creator>Khan, Akram</creator><creator>Makley, Amy T</creator><creator>Hamad, Yasir</creator><creator>Salata, Robert A</creator><creator>Silveira, Fernanda P</creator><creator>Sims, Matthew D</creator><creator>Kabchi, Badih A</creator><creator>Saad, Mohamed A</creator><creator>Brown, Carrie</creator><creator>Oler, Jr, Randolph E</creator><creator>Fowler, Jr, Vance</creator><creator>Wunderink, Richard G</creator><general>American Society for Microbiology</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>5PM</scope><orcidid>https://orcid.org/0000-0002-4730-0655</orcidid><orcidid>https://orcid.org/0000-0001-6616-7127</orcidid></search><sort><creationdate>20210217</creationdate><title>Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)</title><author>Lodise, Thomas P ; Van Wart, Scott ; Sund, Zoe M ; Bressler, Adam M ; Khan, Akram ; Makley, Amy T ; Hamad, Yasir ; Salata, Robert A ; Silveira, Fernanda P ; Sims, Matthew D ; Kabchi, Badih A ; Saad, Mohamed A ; Brown, Carrie ; Oler, Jr, Randolph E ; Fowler, Jr, Vance ; Wunderink, Richard G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a3330-df9acdb22c0f049030fcf75c914fd0315dfbabe084d0c6eb47ac400608caaf7a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acinetobacter baumannii</topic><topic>Adult</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Clinical Therapeutics</topic><topic>Critical Illness</topic><topic>Humans</topic><topic>Microbial Sensitivity Tests</topic><topic>Minocycline</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lodise, Thomas P</creatorcontrib><creatorcontrib>Van Wart, Scott</creatorcontrib><creatorcontrib>Sund, Zoe M</creatorcontrib><creatorcontrib>Bressler, Adam M</creatorcontrib><creatorcontrib>Khan, Akram</creatorcontrib><creatorcontrib>Makley, Amy T</creatorcontrib><creatorcontrib>Hamad, Yasir</creatorcontrib><creatorcontrib>Salata, Robert A</creatorcontrib><creatorcontrib>Silveira, Fernanda P</creatorcontrib><creatorcontrib>Sims, Matthew D</creatorcontrib><creatorcontrib>Kabchi, Badih A</creatorcontrib><creatorcontrib>Saad, Mohamed A</creatorcontrib><creatorcontrib>Brown, Carrie</creatorcontrib><creatorcontrib>Oler, Jr, Randolph E</creatorcontrib><creatorcontrib>Fowler, Jr, Vance</creatorcontrib><creatorcontrib>Wunderink, Richard G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lodise, Thomas P</au><au>Van Wart, Scott</au><au>Sund, Zoe M</au><au>Bressler, Adam M</au><au>Khan, Akram</au><au>Makley, Amy T</au><au>Hamad, Yasir</au><au>Salata, Robert A</au><au>Silveira, Fernanda P</au><au>Sims, Matthew D</au><au>Kabchi, Badih A</au><au>Saad, Mohamed A</au><au>Brown, Carrie</au><au>Oler, Jr, Randolph E</au><au>Fowler, Jr, Vance</au><au>Wunderink, Richard G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2021-02-17</date><risdate>2021</risdate><volume>65</volume><issue>3</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR)
Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [
AUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of
were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f
) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f
). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with
infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>33168615</pmid><doi>10.1128/AAC.01809-20</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-4730-0655</orcidid><orcidid>https://orcid.org/0000-0001-6616-7127</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acinetobacter baumannii Adult Animals Anti-Bacterial Agents - therapeutic use Clinical Therapeutics Critical Illness Humans Microbial Sensitivity Tests Minocycline |
title | Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN) |
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