Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients
Identifieur interne : 000596 ( Main/Exploration ); précédent : 000595; suivant : 000597Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients
Auteurs : Abdulaziz S. Alobaid [Australie, Arabie saoudite] ; Steven C. Wallis [Australie] ; Paul Jarrett [Australie] ; Therese Starr [Australie] ; Janine Stuart [Australie] ; Melissa Lassig-Smith [Australie] ; Jenny Lisette Ord Ez Mejia [Australie] ; Michael S. Roberts [Australie] ; Claire Roger [Australie, France] ; Andrew A. Udy [Australie] ; Jeffrey Lipman [Australie] ; Jason A. Roberts [Australie]Source :
- Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2017.
Descripteurs français
- KwdFr :
- Acide pénicillanique (analogues et dérivés), Acide pénicillanique (pharmacocinétique), Acide pénicillanique (sang), Adulte, Adulte d'âge moyen, Antibactériens (pharmacocinétique), Antibactériens (sang), Biodisponibilité, Calcul des posologies, Calendrier d'administration des médicaments, Créatinine (sang), Femelle, Humains, Indice de masse corporelle, Infections bactériennes (), Infections bactériennes (microbiologie), Infections bactériennes (sang), Infections bactériennes (traitement médicamenteux), Maladie grave, Modèles linéaires, Mâle, Méthode de Monte-Carlo, Obésité morbide (), Obésité morbide (microbiologie), Obésité morbide (sang), Obésité morbide (traitement médicamenteux), Perfusions veineuses, Pipéracilline (pharmacocinétique), Pipéracilline (sang), Sujet âgé, Tests de sensibilité microbienne.
- MESH :
- analogues et dérivés : Acide pénicillanique.
- microbiologie : Infections bactériennes, Obésité morbide.
- pharmacocinétique : Acide pénicillanique, Antibactériens, Pipéracilline.
- sang : Acide pénicillanique, Antibactériens, Créatinine, Infections bactériennes, Obésité morbide, Pipéracilline.
- traitement médicamenteux : Infections bactériennes, Obésité morbide.
- Adulte, Adulte d'âge moyen, Biodisponibilité, Calcul des posologies, Calendrier d'administration des médicaments, Femelle, Humains, Indice de masse corporelle, Infections bactériennes, Maladie grave, Modèles linéaires, Mâle, Méthode de Monte-Carlo, Obésité morbide, Perfusions veineuses, Sujet âgé, Tests de sensibilité microbienne.
English descriptors
- KwdEn :
- Adult, Aged, Anti-Bacterial Agents (blood), Anti-Bacterial Agents (pharmacokinetics), Bacterial Infections (blood), Bacterial Infections (complications), Bacterial Infections (drug therapy), Bacterial Infections (microbiology), Biological Availability, Body Mass Index, Creatinine (blood), Critical Illness, Drug Administration Schedule, Drug Dosage Calculations, Female, Humans, Infusions, Intravenous, Linear Models, Male, Microbial Sensitivity Tests, Middle Aged, Monte Carlo Method, Obesity, Morbid (blood), Obesity, Morbid (complications), Obesity, Morbid (drug therapy), Obesity, Morbid (microbiology), Penicillanic Acid (analogs & derivatives), Penicillanic Acid (blood), Penicillanic Acid (pharmacokinetics), Piperacillin (blood), Piperacillin (pharmacokinetics).
- MESH :
- chemical , analogs & derivatives : Penicillanic Acid.
- chemical , blood : Anti-Bacterial Agents, Creatinine, Penicillanic Acid, Piperacillin.
- chemical , pharmacokinetics : Anti-Bacterial Agents, Penicillanic Acid, Piperacillin.
- blood : Bacterial Infections, Obesity, Morbid.
- complications : Bacterial Infections, Obesity, Morbid.
- drug therapy : Bacterial Infections, Obesity, Morbid.
- microbiology : Bacterial Infections, Obesity, Morbid.
- Adult, Aged, Biological Availability, Body Mass Index, Critical Illness, Drug Administration Schedule, Drug Dosage Calculations, Female, Humans, Infusions, Intravenous, Linear Models, Male, Microbial Sensitivity Tests, Middle Aged, Monte Carlo Method.
Abstract
The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h−1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h−1. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.
Url:
DOI: 10.1128/AAC.01276-16
PubMed: 28052849
PubMed Central: 5328553
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients</title>
<author><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S." last="Alobaid">Abdulaziz S. Alobaid</name>
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<author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name>
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<author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name>
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<author><name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name>
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<author><name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name>
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<author><name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name>
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<author><name sortKey="Udy, Andrew A" sort="Udy, Andrew A" uniqKey="Udy A" first="Andrew A." last="Udy">Andrew A. Udy</name>
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</affiliation>
</author>
<author><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6">Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Antimicrobial Agents and Chemotherapy</title>
<idno type="ISSN">0066-4804</idno>
<idno type="eISSN">1098-6596</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Anti-Bacterial Agents (blood)</term>
<term>Anti-Bacterial Agents (pharmacokinetics)</term>
<term>Bacterial Infections (blood)</term>
<term>Bacterial Infections (complications)</term>
<term>Bacterial Infections (drug therapy)</term>
<term>Bacterial Infections (microbiology)</term>
<term>Biological Availability</term>
<term>Body Mass Index</term>
<term>Creatinine (blood)</term>
<term>Critical Illness</term>
<term>Drug Administration Schedule</term>
<term>Drug Dosage Calculations</term>
<term>Female</term>
<term>Humans</term>
<term>Infusions, Intravenous</term>
<term>Linear Models</term>
<term>Male</term>
<term>Microbial Sensitivity Tests</term>
<term>Middle Aged</term>
<term>Monte Carlo Method</term>
<term>Obesity, Morbid (blood)</term>
<term>Obesity, Morbid (complications)</term>
<term>Obesity, Morbid (drug therapy)</term>
<term>Obesity, Morbid (microbiology)</term>
<term>Penicillanic Acid (analogs & derivatives)</term>
<term>Penicillanic Acid (blood)</term>
<term>Penicillanic Acid (pharmacokinetics)</term>
<term>Piperacillin (blood)</term>
<term>Piperacillin (pharmacokinetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Acide pénicillanique (analogues et dérivés)</term>
<term>Acide pénicillanique (pharmacocinétique)</term>
<term>Acide pénicillanique (sang)</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Antibactériens (pharmacocinétique)</term>
<term>Antibactériens (sang)</term>
<term>Biodisponibilité</term>
<term>Calcul des posologies</term>
<term>Calendrier d'administration des médicaments</term>
<term>Créatinine (sang)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Indice de masse corporelle</term>
<term>Infections bactériennes ()</term>
<term>Infections bactériennes (microbiologie)</term>
<term>Infections bactériennes (sang)</term>
<term>Infections bactériennes (traitement médicamenteux)</term>
<term>Maladie grave</term>
<term>Modèles linéaires</term>
<term>Mâle</term>
<term>Méthode de Monte-Carlo</term>
<term>Obésité morbide ()</term>
<term>Obésité morbide (microbiologie)</term>
<term>Obésité morbide (sang)</term>
<term>Obésité morbide (traitement médicamenteux)</term>
<term>Perfusions veineuses</term>
<term>Pipéracilline (pharmacocinétique)</term>
<term>Pipéracilline (sang)</term>
<term>Sujet âgé</term>
<term>Tests de sensibilité microbienne</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Penicillanic Acid</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Creatinine</term>
<term>Penicillanic Acid</term>
<term>Piperacillin</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-Bacterial Agents</term>
<term>Penicillanic Acid</term>
<term>Piperacillin</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Acide pénicillanique</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Bacterial Infections</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Bacterial Infections</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Bacterial Infections</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections bactériennes</term>
<term>Obésité morbide</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Bacterial Infections</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Acide pénicillanique</term>
<term>Antibactériens</term>
<term>Pipéracilline</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Acide pénicillanique</term>
<term>Antibactériens</term>
<term>Créatinine</term>
<term>Infections bactériennes</term>
<term>Obésité morbide</term>
<term>Pipéracilline</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections bactériennes</term>
<term>Obésité morbide</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Biological Availability</term>
<term>Body Mass Index</term>
<term>Critical Illness</term>
<term>Drug Administration Schedule</term>
<term>Drug Dosage Calculations</term>
<term>Female</term>
<term>Humans</term>
<term>Infusions, Intravenous</term>
<term>Linear Models</term>
<term>Male</term>
<term>Microbial Sensitivity Tests</term>
<term>Middle Aged</term>
<term>Monte Carlo Method</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Biodisponibilité</term>
<term>Calcul des posologies</term>
<term>Calendrier d'administration des médicaments</term>
<term>Femelle</term>
<term>Humains</term>
<term>Indice de masse corporelle</term>
<term>Infections bactériennes</term>
<term>Maladie grave</term>
<term>Modèles linéaires</term>
<term>Mâle</term>
<term>Méthode de Monte-Carlo</term>
<term>Obésité morbide</term>
<term>Perfusions veineuses</term>
<term>Sujet âgé</term>
<term>Tests de sensibilité microbienne</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m<sup>2</sup>
, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h<sup>−1</sup>
, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h<sup>−1</sup>
. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Arabie saoudite</li>
<li>Australie</li>
<li>France</li>
</country>
<region><li>Languedoc-Roussillon</li>
<li>Occitanie (région administrative)</li>
</region>
<settlement><li>Nîmes</li>
</settlement>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S." last="Alobaid">Abdulaziz S. Alobaid</name>
</noRegion>
<name sortKey="Jarrett, Paul" sort="Jarrett, Paul" uniqKey="Jarrett P" first="Paul" last="Jarrett">Paul Jarrett</name>
<name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name>
<name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name>
<name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name>
<name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name>
<name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name>
<name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name>
<name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name>
<name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name>
<name sortKey="Roberts, Michael S" sort="Roberts, Michael S" uniqKey="Roberts M" first="Michael S." last="Roberts">Michael S. Roberts</name>
<name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name>
<name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name>
<name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name>
<name sortKey="Udy, Andrew A" sort="Udy, Andrew A" uniqKey="Udy A" first="Andrew A." last="Udy">Andrew A. Udy</name>
<name sortKey="Udy, Andrew A" sort="Udy, Andrew A" uniqKey="Udy A" first="Andrew A." last="Udy">Andrew A. Udy</name>
<name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name>
</country>
<country name="Arabie saoudite"><noRegion><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S." last="Alobaid">Abdulaziz S. Alobaid</name>
</noRegion>
</country>
<country name="France"><region name="Occitanie (région administrative)"><name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name>
</region>
</country>
</tree>
</affiliations>
</record>
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