title: Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia.
abstract: OBJECTIVE
  The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing.
  
  
  METHODS
  We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays<500ng/mL were considered as under dosed.
  
  
  RESULTS
  Fifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375ng/mL (<200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003).
  
  
  CONCLUSIONS
  This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.
authors.affiliation: Service de pharmacie clinique, Institut Gustave-Roussy, 94805 Villejuif cedex, France.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Desplanques
authors.affiliation: Service d'hématologie, Institut Gustave Roussy, 94805 Villejuif cedex, France.
authors.forename: R
authors.initials: R
authors.lastname: Burlacu
authors.affiliation: Service de pharmacologie et toxicologie, Hôpital Européen George-Pompidou, 75015 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Poinsignon
authors.affiliation: Service d'hématologie, Institut Gustave Roussy, 94805 Villejuif cedex, France.
authors.forename: H
authors.initials: H
authors.lastname: Boussion
authors.affiliation: Service de biostatistique et d'épidémiologie, Institut Gustave-Roussy, université Paris-Sud, 94805 Villejuif cedex, France.
authors.forename: I
authors.initials: I
authors.lastname: Borget
authors.affiliation: Service de maladies infectieuses, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France.
authors.forename: B
authors.initials: B
authors.lastname: Wyplosz
authors.affiliation: Service d'hématologie, Institut Gustave Roussy, 94805 Villejuif cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: de Botton
authors.affiliation: Service de pharmacologie et toxicologie, Hôpital Européen George-Pompidou, 75015 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Billaud
authors.affiliation: Service de microbiologie, Institut Gustave-Roussy, 94805 Villejuif cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Chachaty
authors.affiliation: Département de soins aigus, Institut Gustave-Roussy, 94805 Villejuif cedex, France.
authors.forename: B
authors.initials: B
authors.lastname: Gachot
authors.affiliation: Service de pharmacie clinique, Institut Gustave-Roussy, 94805 Villejuif cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Netzer
authors.affiliation: Service d'hématologie, Institut Gustave Roussy, 94805 Villejuif cedex, France. Electronic address: jeanbaptiste.micol@gustaveroussy.fr.
authors.forename: J-B
authors.initials: JB
authors.lastname: Micol
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood*; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: Acute myeloid leukemia; Aspergillose invasive; Drug interactions; Interaction médicamenteuse; Invasive aspergillosis; Leucémie aiguë myéloïde; Posaconazole