RapamycinFungusV1, Main, Exploration, bibRecord, 000522

Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

Identifieur interne : 000522 ( Main/Exploration ); précédent : 000521; suivant : 000523

Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

Auteurs : Manon Launay [France] ; Antoine Roux [France] ; Laurence Beaumont [France] ; Benoit Douvry [France] ; Lucien Lecuyer [France] ; Emmanuel Douez [France] ; Clément Picard [France] ; Dominique Grenet [France] ; Vincent Jullien [France] ; Véronique Boussaud [France] ; Romain Guillemain [France] ; Eliane M. Billaud [France]

Source :

Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2018.

RBID : pubmed:29311077

Descripteurs français

KwdFr :
- Adulte (MeSH), Adulte d'âge moyen (MeSH), Antifongiques (pharmacocinétique), Antifongiques (pharmacologie), Antifongiques (sang), Aspergillose pulmonaire invasive (chirurgie), Aspergillose pulmonaire invasive (immunologie), Aspergillose pulmonaire invasive (microbiologie), Aspergillose pulmonaire invasive (prévention et contrôle), Aspergillus (effets des médicaments et des substances chimiques), Calendrier d'administration des médicaments (MeSH), Comprimés (MeSH), Femelle (MeSH), Humains (MeSH), Immunosuppresseurs (sang), Immunosuppresseurs (usage thérapeutique), Interactions médicamenteuses (MeSH), Mucoviscidose (chirurgie), Mucoviscidose (immunologie), Mucoviscidose (microbiologie), Mucoviscidose (traitement médicamenteux), Mâle (MeSH), Sujet âgé (MeSH), Tacrolimus (sang), Tacrolimus (usage thérapeutique), Transplantation pulmonaire (MeSH), Triazoles (pharmacocinétique), Triazoles (pharmacologie), Triazoles (sang), Études prospectives (MeSH), Évérolimus (sang), Évérolimus (usage thérapeutique).
MESH :
- chirurgie : Aspergillose pulmonaire invasive, Mucoviscidose.
- effets des médicaments et des substances chimiques : Aspergillus.
- immunologie : Aspergillose pulmonaire invasive, Mucoviscidose.
- microbiologie : Aspergillose pulmonaire invasive, Mucoviscidose.
- pharmacocinétique : Antifongiques, Triazoles.
- pharmacologie : Antifongiques, Triazoles.
- prévention et contrôle : Aspergillose pulmonaire invasive.
- sang : Antifongiques, Immunosuppresseurs, Tacrolimus, Triazoles, Évérolimus.
- traitement médicamenteux : Mucoviscidose.
- usage thérapeutique : Immunosuppresseurs, Tacrolimus, Évérolimus.
- Adulte, Adulte d'âge moyen, Calendrier d'administration des médicaments, Comprimés, Femelle, Humains, Interactions médicamenteuses, Mâle, Sujet âgé, Transplantation pulmonaire, Études prospectives.

English descriptors

KwdEn :
- Adult (MeSH), Aged (MeSH), Antifungal Agents (blood), Antifungal Agents (pharmacokinetics), Antifungal Agents (pharmacology), Aspergillus (drug effects), Cystic Fibrosis (drug therapy), Cystic Fibrosis (immunology), Cystic Fibrosis (microbiology), Cystic Fibrosis (surgery), Drug Administration Schedule (MeSH), Drug Interactions (MeSH), Everolimus (blood), Everolimus (therapeutic use), Female (MeSH), Humans (MeSH), Immunosuppressive Agents (blood), Immunosuppressive Agents (therapeutic use), Invasive Pulmonary Aspergillosis (immunology), Invasive Pulmonary Aspergillosis (microbiology), Invasive Pulmonary Aspergillosis (prevention & control), Invasive Pulmonary Aspergillosis (surgery), Lung Transplantation (MeSH), Male (MeSH), Middle Aged (MeSH), Prospective Studies (MeSH), Tablets (MeSH), Tacrolimus (blood), Tacrolimus (therapeutic use), Triazoles (blood), Triazoles (pharmacokinetics), Triazoles (pharmacology).
MESH :
- chemical , blood : Antifungal Agents, Everolimus, Immunosuppressive Agents, Tacrolimus, Triazoles.
- chemical , pharmacokinetics : Antifungal Agents, Triazoles.
- chemical , pharmacology : Antifungal Agents, Triazoles.
- drug effects : Aspergillus.
- drug therapy : Cystic Fibrosis.
- immunology : Cystic Fibrosis, Invasive Pulmonary Aspergillosis.
- microbiology : Cystic Fibrosis, Invasive Pulmonary Aspergillosis.
- prevention & control : Invasive Pulmonary Aspergillosis.
- surgery : Cystic Fibrosis, Invasive Pulmonary Aspergillosis.
- chemical , therapeutic use : Everolimus, Immunosuppressive Agents, Tacrolimus.
- Adult, Aged, Drug Administration Schedule, Drug Interactions, Female, Humans, Lung Transplantation, Male, Middle Aged, Prospective Studies, Tablets.

Abstract

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations (C₀) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) C₀ measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively (P = 0.001* [asterisk means that statistical test is significant]), and the PSZ C₀ exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively (P < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL C₀/dose ratio (C₀/D) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution (P = 0.034*). The ERL C₀/D was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; P = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.

DOI: 10.1128/AAC.02061-17
PubMed: 29311077
PubMed Central: PMC5826104

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000643
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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.</title>
<author><name sortKey="Launay, Manon" sort="Launay, Manon" uniqKey="Launay M" first="Manon" last="Launay">Manon Launay</name>
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<settlement type="city">Paris</settlement>
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<author><name sortKey="Roux, Antoine" sort="Roux, Antoine" uniqKey="Roux A" first="Antoine" last="Roux">Antoine Roux</name>
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<author><name sortKey="Beaumont, Laurence" sort="Beaumont, Laurence" uniqKey="Beaumont L" first="Laurence" last="Beaumont">Laurence Beaumont</name>
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<author><name sortKey="Douvry, Benoit" sort="Douvry, Benoit" uniqKey="Douvry B" first="Benoit" last="Douvry">Benoit Douvry</name>
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<country xml:lang="fr">France</country>
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<wicri:noRegion>Suresnes</wicri:noRegion>
<wicri:noRegion>Suresnes</wicri:noRegion>
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<author><name sortKey="Lecuyer, Lucien" sort="Lecuyer, Lucien" uniqKey="Lecuyer L" first="Lucien" last="Lecuyer">Lucien Lecuyer</name>
<affiliation wicri:level="3"><nlm:affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
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<author><name sortKey="Douez, Emmanuel" sort="Douez, Emmanuel" uniqKey="Douez E" first="Emmanuel" last="Douez">Emmanuel Douez</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Picard, Clement" sort="Picard, Clement" uniqKey="Picard C" first="Clément" last="Picard">Clément Picard</name>
<affiliation wicri:level="1"><nlm:affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes</wicri:regionArea>
<wicri:noRegion>Suresnes</wicri:noRegion>
<wicri:noRegion>Suresnes</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Grenet, Dominique" sort="Grenet, Dominique" uniqKey="Grenet D" first="Dominique" last="Grenet">Dominique Grenet</name>
<affiliation wicri:level="1"><nlm:affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes</wicri:regionArea>
<wicri:noRegion>Suresnes</wicri:noRegion>
<wicri:noRegion>Suresnes</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jullien, Vincent" sort="Jullien, Vincent" uniqKey="Jullien V" first="Vincent" last="Jullien">Vincent Jullien</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Boussaud, Veronique" sort="Boussaud, Veronique" uniqKey="Boussaud V" first="Véronique" last="Boussaud">Véronique Boussaud</name>
<affiliation wicri:level="3"><nlm:affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Guillemain, Romain" sort="Guillemain, Romain" uniqKey="Guillemain R" first="Romain" last="Guillemain">Romain Guillemain</name>
<affiliation wicri:level="3"><nlm:affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Billaud, Eliane M" sort="Billaud, Eliane M" uniqKey="Billaud E" first="Eliane M" last="Billaud">Eliane M. Billaud</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France manon.launay@aphp.fr Eliane.billaud@aphp.fr.</nlm:affiliation>
<country wicri:rule="url">France</country>
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<region type="old region">Île-de-France</region>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Antifungal Agents (blood)</term>
<term>Antifungal Agents (pharmacokinetics)</term>
<term>Antifungal Agents (pharmacology)</term>
<term>Aspergillus (drug effects)</term>
<term>Cystic Fibrosis (drug therapy)</term>
<term>Cystic Fibrosis (immunology)</term>
<term>Cystic Fibrosis (microbiology)</term>
<term>Cystic Fibrosis (surgery)</term>
<term>Drug Administration Schedule (MeSH)</term>
<term>Drug Interactions (MeSH)</term>
<term>Everolimus (blood)</term>
<term>Everolimus (therapeutic use)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Immunosuppressive Agents (blood)</term>
<term>Immunosuppressive Agents (therapeutic use)</term>
<term>Invasive Pulmonary Aspergillosis (immunology)</term>
<term>Invasive Pulmonary Aspergillosis (microbiology)</term>
<term>Invasive Pulmonary Aspergillosis (prevention & control)</term>
<term>Invasive Pulmonary Aspergillosis (surgery)</term>
<term>Lung Transplantation (MeSH)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Prospective Studies (MeSH)</term>
<term>Tablets (MeSH)</term>
<term>Tacrolimus (blood)</term>
<term>Tacrolimus (therapeutic use)</term>
<term>Triazoles (blood)</term>
<term>Triazoles (pharmacokinetics)</term>
<term>Triazoles (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Antifongiques (pharmacocinétique)</term>
<term>Antifongiques (pharmacologie)</term>
<term>Antifongiques (sang)</term>
<term>Aspergillose pulmonaire invasive (chirurgie)</term>
<term>Aspergillose pulmonaire invasive (immunologie)</term>
<term>Aspergillose pulmonaire invasive (microbiologie)</term>
<term>Aspergillose pulmonaire invasive (prévention et contrôle)</term>
<term>Aspergillus (effets des médicaments et des substances chimiques)</term>
<term>Calendrier d'administration des médicaments (MeSH)</term>
<term>Comprimés (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Immunosuppresseurs (sang)</term>
<term>Immunosuppresseurs (usage thérapeutique)</term>
<term>Interactions médicamenteuses (MeSH)</term>
<term>Mucoviscidose (chirurgie)</term>
<term>Mucoviscidose (immunologie)</term>
<term>Mucoviscidose (microbiologie)</term>
<term>Mucoviscidose (traitement médicamenteux)</term>
<term>Mâle (MeSH)</term>
<term>Sujet âgé (MeSH)</term>
<term>Tacrolimus (sang)</term>
<term>Tacrolimus (usage thérapeutique)</term>
<term>Transplantation pulmonaire (MeSH)</term>
<term>Triazoles (pharmacocinétique)</term>
<term>Triazoles (pharmacologie)</term>
<term>Triazoles (sang)</term>
<term>Études prospectives (MeSH)</term>
<term>Évérolimus (sang)</term>
<term>Évérolimus (usage thérapeutique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antifungal Agents</term>
<term>Everolimus</term>
<term>Immunosuppressive Agents</term>
<term>Tacrolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antifungal Agents</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antifungal Agents</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="chirurgie" xml:lang="fr"><term>Aspergillose pulmonaire invasive</term>
<term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Aspergillus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Cystic Fibrosis</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Aspergillus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Aspergillose pulmonaire invasive</term>
<term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cystic Fibrosis</term>
<term>Invasive Pulmonary Aspergillosis</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Aspergillose pulmonaire invasive</term>
<term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Cystic Fibrosis</term>
<term>Invasive Pulmonary Aspergillosis</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Antifongiques</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antifongiques</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Invasive Pulmonary Aspergillosis</term>
</keywords>
<keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Aspergillose pulmonaire invasive</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Antifongiques</term>
<term>Immunosuppresseurs</term>
<term>Tacrolimus</term>
<term>Triazoles</term>
<term>Évérolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Cystic Fibrosis</term>
<term>Invasive Pulmonary Aspergillosis</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Everolimus</term>
<term>Immunosuppressive Agents</term>
<term>Tacrolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Mucoviscidose</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Immunosuppresseurs</term>
<term>Tacrolimus</term>
<term>Évérolimus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Drug Administration Schedule</term>
<term>Drug Interactions</term>
<term>Female</term>
<term>Humans</term>
<term>Lung Transplantation</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Prospective Studies</term>
<term>Tablets</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Calendrier d'administration des médicaments</term>
<term>Comprimés</term>
<term>Femelle</term>
<term>Humains</term>
<term>Interactions médicamenteuses</term>
<term>Mâle</term>
<term>Sujet âgé</term>
<term>Transplantation pulmonaire</term>
<term>Études prospectives</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations (<i>C</i>
<sub>0</sub>
) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) <i>C</i>
<sub>0</sub>
 measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively (<i>P</i>
 = 0.001* [asterisk means that statistical test is significant]), and the PSZ <i>C</i>
<sub>0</sub>
 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively (<i>P</i>
 < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL <i>C</i>
<sub>0</sub>
/dose ratio (<i>C</i>
<sub>0</sub>
/<i>D</i>
) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution (<i>P</i>
 = 0.034*). The ERL <i>C</i>
<sub>0</sub>
/<i>D</i>
 was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; <i>P</i>
 = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29311077</PMID>
<DateCompleted><Year>2019</Year>
<Month>05</Month>
<Day>14</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>05</Month>
<Day>14</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-6596</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>62</Volume>
<Issue>3</Issue>
<PubDate><Year>2018</Year>
<Month>03</Month>
</PubDate>
</JournalIssue>
<Title>Antimicrobial agents and chemotherapy</Title>
<ISOAbbreviation>Antimicrob Agents Chemother</ISOAbbreviation>
</Journal>
<ArticleTitle>Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">e02061-17</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/AAC.02061-17</ELocationID>
<Abstract><AbstractText>Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations (<i>C</i>
<sub>0</sub>
) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) <i>C</i>
<sub>0</sub>
 measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively (<i>P</i>
 = 0.001* [asterisk means that statistical test is significant]), and the PSZ <i>C</i>
<sub>0</sub>
 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively (<i>P</i>
 < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL <i>C</i>
<sub>0</sub>
/dose ratio (<i>C</i>
<sub>0</sub>
/<i>D</i>
) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution (<i>P</i>
 = 0.034*). The ERL <i>C</i>
<sub>0</sub>
/<i>D</i>
 was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; <i>P</i>
 = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.</AbstractText>
<CopyrightInformation>Copyright © 2018 American Society for Microbiology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Launay</LastName>
<ForeName>Manon</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0003-3113-7301</Identifier>
<AffiliationInfo><Affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France manon.launay@aphp.fr Eliane.billaud@aphp.fr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Roux</LastName>
<ForeName>Antoine</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Université Versailles Saint-Quentin, Versailles, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Beaumont</LastName>
<ForeName>Laurence</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Douvry</LastName>
<ForeName>Benoit</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lecuyer</LastName>
<ForeName>Lucien</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Douez</LastName>
<ForeName>Emmanuel</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Picard</LastName>
<ForeName>Clément</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Grenet</LastName>
<ForeName>Dominique</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department, Foch Hospital, Suresnes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jullien</LastName>
<ForeName>Vincent</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Boussaud</LastName>
<ForeName>Véronique</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guillemain</LastName>
<ForeName>Romain</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Thoracic Transplantation, European Hospital Georges Pompidou-APHP, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Billaud</LastName>
<ForeName>Eliane M</ForeName>
<Initials>EM</Initials>
<AffiliationInfo><Affiliation>Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou-APHP, Paris, France manon.launay@aphp.fr Eliane.billaud@aphp.fr.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D016448">Multicenter Study</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2018</Year>
<Month>02</Month>
<Day>23</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Antimicrob Agents Chemother</MedlineTA>
<NlmUniqueID>0315061</NlmUniqueID>
<ISSNLinking>0066-4804</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000935">Antifungal Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D013607">Tablets</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014230">Triazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>6TK1G07BHZ</RegistryNumber>
<NameOfSubstance UI="C101425">posaconazole</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>9HW64Q8G6G</RegistryNumber>
<NameOfSubstance UI="D000068338">Everolimus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>WM0HAQ4WNM</RegistryNumber>
<NameOfSubstance UI="D016559">Tacrolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000935" MajorTopicYN="N">Antifungal Agents</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001230" MajorTopicYN="N">Aspergillus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003550" MajorTopicYN="N">Cystic Fibrosis</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
<QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004334" MajorTopicYN="N">Drug Administration Schedule</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004347" MajorTopicYN="N">Drug Interactions</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000068338" MajorTopicYN="N">Everolimus</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007166" MajorTopicYN="N">Immunosuppressive Agents</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055744" MajorTopicYN="N">Invasive Pulmonary Aspergillosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
<QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016040" MajorTopicYN="Y">Lung Transplantation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013607" MajorTopicYN="N">Tablets</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016559" MajorTopicYN="N">Tacrolimus</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014230" MajorTopicYN="N">Triazoles</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">cystic fibrosis</Keyword>
<Keyword MajorTopicYN="Y">drug-drug interaction</Keyword>
<Keyword MajorTopicYN="Y">lung transplantation</Keyword>
<Keyword MajorTopicYN="Y">posaconazole tablets</Keyword>
<Keyword MajorTopicYN="Y">proton pump inhibitors</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year>
<Month>10</Month>
<Day>09</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>12</Month>
<Day>14</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2018</Year>
<Month>1</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2019</Year>
<Month>5</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2018</Year>
<Month>1</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">29311077</ArticleId>
<ArticleId IdType="pii">AAC.02061-17</ArticleId>
<ArticleId IdType="doi">10.1128/AAC.02061-17</ArticleId>
<ArticleId IdType="pmc">PMC5826104</ArticleId>
</ArticleIdList>
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	Serveur d'exploration sur la rapamycine et les champignons
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Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

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