{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:10:49Z","timestamp":1784164249108,"version":"3.55.0"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Posaconazole (PCZ) is the latest triazole antifungal agent that has been approved for prophylaxis of invasive aspergillosis in high-risk immunocompromised patients, such as allogeneic hematopoietic stem cell transplantation patients, who develop graft-versus-host disease (GVHD). PCZ has high interindividual variability with regard to its plasma drug trough concentrations (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            ). Moreover, the concentration-efficiency relationship remains to be better characterized in prophylaxis. To determine the variability factors in plasma drug concentrations, the PCZ\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            and clinical parameters (localization of GVHD, presence of diarrhea, and diagnosis of invasive aspergillosis) were collected retrospectively in 29 consecutive allogeneic hematopoietic stem cell transplantation patients who developed GVHD and were receiving prophylactic PCZ (200 mg, 3 times\/day, for \u22657 days). Blood samples were analyzed at steady state to determine the PCZ\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            by liquid chromatography-tandem mass spectrometry. The average PCZ\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            was 1.28 \u00b1 0.82 mg\/liter (mean \u00b1 standard deviation;\n            <jats:italic>n<\/jats:italic>\n            = 292 dosages), with an intraindividual variability of 49% and an interindividual variability of 64%. Twenty percent of\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            s were below 0.7 mg\/liter, which is considered the threshold of efficacy by the Food and Drug Administration. The patients who had gastrointestinal (GI) GVHD experienced a 24% reduction in the posaconazole\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            , compared with those with other localizations of GVHD. This decrease reached 33% when patients presented with diarrhea due to GI GVHD or an infectious etiology. PCZ\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            s were 26% lower when invasive aspergillosis was declared. These data demonstrate that GI disturbances affect drug concentrations. Thus, therapeutic monitoring of PCZ can be used to detect low drug concentrations, possibly resulting in a lack of efficacy of invasive aspergillosis prophylaxis.\n          <\/jats:p>","DOI":"10.1128\/aac.00815-12","type":"journal-article","created":{"date-parts":[[2012,7,31]],"date-time":"2012-07-31T07:47:26Z","timestamp":1343720846000},"page":"5247-5252","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Therapeutic Drug Monitoring of Posaconazole in Allogeneic Hematopoietic Stem Cell Transplantation Patients Who Develop Gastrointestinal Graft-versus-Host Disease"],"prefix":"10.1128","volume":"56","author":[{"given":"J.","family":"Tonini","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Department of Biochemistry, Toxicology and Pharmacology, University Hospital Grenoble, Grenoble, France"},{"name":"INSERM U1042, Hypoxia Physiopathology Laboratory, Joseph Fourier University, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Thi\u00e9baut","sequence":"additional","affiliation":[{"name":"Hematology Clinic, University Hospital Grenoble, Grenoble, France"},{"name":"UMR 5525, CNRS, Joseph Fourier University, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. F.","family":"Jourdil","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Department of Biochemistry, Toxicology and Pharmacology, University Hospital Grenoble, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. S.","family":"Berruyer","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Department of Biochemistry, Toxicology and Pharmacology, University Hospital Grenoble, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. E.","family":"Bulabois","sequence":"additional","affiliation":[{"name":"Hematology Clinic, University Hospital Grenoble, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Y.","family":"Cahn","sequence":"additional","affiliation":[{"name":"Hematology Clinic, University Hospital Grenoble, Grenoble, France"},{"name":"UMR 5525, CNRS, Joseph Fourier University, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Stanke-Labesque","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Department of Biochemistry, Toxicology and Pharmacology, University Hospital Grenoble, Grenoble, France"},{"name":"INSERM U1042, Hypoxia Physiopathology Laboratory, Joseph Fourier University, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00705-08"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.11.021"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061094"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01977.x"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) C","volume":"46","author":"De Pauw B","year":"2008","unstructured":"De PauwB. 2008. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) C. Clin. Infect. Dis. 46:1813\u20131821.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544020-00006"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.bbmt.2005.09.004","article-title":"National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. I. Diagnosis and staging working group report","volume":"11","author":"Filipovich AH","year":"2005","unstructured":"FilipovichAH. 2005. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. I. Diagnosis and staging working group report. Biol. Blood Marrow Transplant. 11:945\u2013956.","journal-title":"Biol. Blood Marrow Transplant."},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.64"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01027-09"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.28.10.1223"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.12.1627"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01034-08"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00939-09"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.2165\/11319340-000000000-00000"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05219-11"},{"key":"e_1_3_1_17_2","first-page":"825","article-title":"1994 Consensus Conference on Acute GVHD Grading","volume":"15","author":"Przepiorka D","year":"1995","unstructured":"PrzepiorkaD. 1995. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 15:825\u2013828.","journal-title":"Bone Marrow Transplant."},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00240-09"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.658-666.2006"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061098"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/508774"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00815-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00815-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:02:16Z","timestamp":1645480936000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00815-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1128\/AAC.00815-12"],"URL":"https:\/\/doi.org\/10.1128\/aac.00815-12","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]},"assertion":[{"value":"2012-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}