AustralieFrV1, Main, Exploration, bibRecord, 002039

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

Identifieur interne : 002039 ( Main/Exploration ); précédent : 002038; suivant : 002040

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

Auteurs : Abdulaziz S. Alobaid [Australie] ; 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] ; Mahipal G. Sinnollareddy [Australie] ; Claire Roger [Australie, France] ; Jeffrey Lipman [Australie] ; Jason A. Roberts [Australie]

Source :

Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2016.

RBID : PMC:5075058

Descripteurs français

KwdFr :
- Adulte, Adulte d'âge moyen, Aire sous la courbe, Antifongiques (pharmacocinétique), Antifongiques (sang), Calendrier d'administration des médicaments, Candida (), Candida (croissance et développement), Candidose (), Candidose (anatomopathologie), Candidose (microbiologie), Candidose (traitement médicamenteux), Femelle, Fluconazole (pharmacocinétique), Fluconazole (sang), Humains, Indice de masse corporelle, Maladie grave, Modèles statistiques, Mâle, Méthode de Monte-Carlo, Obésité morbide (), Obésité morbide (anatomopathologie), Obésité morbide (microbiologie), Obésité morbide (traitement médicamenteux), Sujet âgé, Tests de sensibilité microbienne, Unités de soins intensifs, Études prospectives.
MESH :
- anatomopathologie : Candidose, Obésité morbide.
- croissance et développement : Candida.
- microbiologie : Candidose, Obésité morbide.
- pharmacocinétique : Antifongiques, Fluconazole.
- sang : Antifongiques, Fluconazole.
- traitement médicamenteux : Candidose, Obésité morbide.
- Adulte, Adulte d'âge moyen, Aire sous la courbe, Calendrier d'administration des médicaments, Candida, Candidose, Femelle, Humains, Indice de masse corporelle, Maladie grave, Modèles statistiques, Mâle, Méthode de Monte-Carlo, Obésité morbide, Sujet âgé, Tests de sensibilité microbienne, Unités de soins intensifs, Études prospectives.

English descriptors

KwdEn :
- Adult, Aged, Antifungal Agents (blood), Antifungal Agents (pharmacokinetics), Area Under Curve, Body Mass Index, Candida (drug effects), Candida (growth & development), Candidiasis (complications), Candidiasis (drug therapy), Candidiasis (microbiology), Candidiasis (pathology), Critical Illness, Drug Administration Schedule, Female, Fluconazole (blood), Fluconazole (pharmacokinetics), Humans, Intensive Care Units, Male, Microbial Sensitivity Tests, Middle Aged, Models, Statistical, Monte Carlo Method, Obesity, Morbid (complications), Obesity, Morbid (drug therapy), Obesity, Morbid (microbiology), Obesity, Morbid (pathology), Prospective Studies.
MESH :
- chemical , blood : Antifungal Agents, Fluconazole.
- chemical , pharmacokinetics : Antifungal Agents, Fluconazole.
- complications : Candidiasis, Obesity, Morbid.
- drug effects : Candida.
- drug therapy : Candidiasis, Obesity, Morbid.
- growth & development : Candida.
- microbiology : Candidiasis, Obesity, Morbid.
- pathology : Candidiasis, Obesity, Morbid.
- Adult, Aged, Area Under Curve, Body Mass Index, Critical Illness, Drug Administration Schedule, Female, Humans, Intensive Care Units, Male, Microbial Sensitivity Tests, Middle Aged, Models, Statistical, Monte Carlo Method, Prospective Studies.

Abstract

Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m²), obese (30.0 to 39.9 kg/m²), and morbidly obese (≥40 kg/m²). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n = 6) and morbidly obese (n = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m², respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (V_c) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m². A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075058

DOI: 10.1128/AAC.01088-16
PubMed: 27550344
PubMed Central: 5075058

Affiliations:

Le document en format XML

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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="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</name>
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<author><name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name>
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</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5">School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Antifungal Agents (blood)</term>
<term>Antifungal Agents (pharmacokinetics)</term>
<term>Area Under Curve</term>
<term>Body Mass Index</term>
<term>Candida (drug effects)</term>
<term>Candida (growth & development)</term>
<term>Candidiasis (complications)</term>
<term>Candidiasis (drug therapy)</term>
<term>Candidiasis (microbiology)</term>
<term>Candidiasis (pathology)</term>
<term>Critical Illness</term>
<term>Drug Administration Schedule</term>
<term>Female</term>
<term>Fluconazole (blood)</term>
<term>Fluconazole (pharmacokinetics)</term>
<term>Humans</term>
<term>Intensive Care Units</term>
<term>Male</term>
<term>Microbial Sensitivity Tests</term>
<term>Middle Aged</term>
<term>Models, Statistical</term>
<term>Monte Carlo Method</term>
<term>Obesity, Morbid (complications)</term>
<term>Obesity, Morbid (drug therapy)</term>
<term>Obesity, Morbid (microbiology)</term>
<term>Obesity, Morbid (pathology)</term>
<term>Prospective Studies</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Aire sous la courbe</term>
<term>Antifongiques (pharmacocinétique)</term>
<term>Antifongiques (sang)</term>
<term>Calendrier d'administration des médicaments</term>
<term>Candida ()</term>
<term>Candida (croissance et développement)</term>
<term>Candidose ()</term>
<term>Candidose (anatomopathologie)</term>
<term>Candidose (microbiologie)</term>
<term>Candidose (traitement médicamenteux)</term>
<term>Femelle</term>
<term>Fluconazole (pharmacocinétique)</term>
<term>Fluconazole (sang)</term>
<term>Humains</term>
<term>Indice de masse corporelle</term>
<term>Maladie grave</term>
<term>Modèles statistiques</term>
<term>Mâle</term>
<term>Méthode de Monte-Carlo</term>
<term>Obésité morbide ()</term>
<term>Obésité morbide (anatomopathologie)</term>
<term>Obésité morbide (microbiologie)</term>
<term>Obésité morbide (traitement médicamenteux)</term>
<term>Sujet âgé</term>
<term>Tests de sensibilité microbienne</term>
<term>Unités de soins intensifs</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antifungal Agents</term>
<term>Fluconazole</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antifungal Agents</term>
<term>Fluconazole</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Candidose</term>
<term>Obésité morbide</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Candidiasis</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Candida</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Candida</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Candidiasis</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Candida</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Candidose</term>
<term>Obésité morbide</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Candidiasis</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Candidiasis</term>
<term>Obesity, Morbid</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Antifongiques</term>
<term>Fluconazole</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Antifongiques</term>
<term>Fluconazole</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Candidose</term>
<term>Obésité morbide</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Area Under Curve</term>
<term>Body Mass Index</term>
<term>Critical Illness</term>
<term>Drug Administration Schedule</term>
<term>Female</term>
<term>Humans</term>
<term>Intensive Care Units</term>
<term>Male</term>
<term>Microbial Sensitivity Tests</term>
<term>Middle Aged</term>
<term>Models, Statistical</term>
<term>Monte Carlo Method</term>
<term>Prospective Studies</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Aire sous la courbe</term>
<term>Calendrier d'administration des médicaments</term>
<term>Candida</term>
<term>Candidose</term>
<term>Femelle</term>
<term>Humains</term>
<term>Indice de masse corporelle</term>
<term>Maladie grave</term>
<term>Modèles statistiques</term>
<term>Mâle</term>
<term>Méthode de Monte-Carlo</term>
<term>Obésité morbide</term>
<term>Sujet âgé</term>
<term>Tests de sensibilité microbienne</term>
<term>Unités de soins intensifs</term>
<term>Études prospectives</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m<sup>2</sup>
), obese (30.0 to 39.9 kg/m<sup>2</sup>
), and morbidly obese (≥40 kg/m<sup>2</sup>
). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (<italic>n</italic>
 = 6) and morbidly obese (<italic>n</italic>
 = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m<sup>2</sup>
, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (<italic>V<sub>c</sub>
</italic>
) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m<sup>2</sup>
. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.</p>
</div>
</front>
</TEI>
<affiliations><list><country><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="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</name>
<name sortKey="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</name>
<name sortKey="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</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="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name>
</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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Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

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