title: Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.
abstract: OBJECTIVE
  Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated.
  
  
  METHODS
  A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis.
  
  
  RESULTS
  Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64).
  
  
  CONCLUSIONS
  Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.
authors.affiliation: Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium. Kim_vanstraelen@hotmail.com.
authors.forename: Kim
authors.initials: K
authors.lastname: Vanstraelen
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria. Juergen.prattes@medunigraz.at.
authors.forename: Juergen
authors.initials: J
authors.lastname: Prattes
authors.affiliation: Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Department of Microbiology and Immunology, Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lagrou
authors.affiliation: Department of Hematology, Acute Leukemia and Stem Cell Transplantation Unit, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Schoemans
authors.affiliation: Department of Microbiology and Immunology, Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Peersman
authors.affiliation: Department of Microbiology and Immunology, Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.|Department of Cardiovascular Sciences, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.affiliation: Department of Hematology, Jessa Hospital Hasselt, Hasselt, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, University Leuven, Leuven, Belgium.
authors.forename: Raf
authors.initials: R
authors.lastname: Mols
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, University Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, University Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.affiliation: Department of Internal Medicine, Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.|Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.|Division of Infectious Diseases, Department of Medicine, University of California, San Diego, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hoenigl
authors.affiliation: Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Isabel
authors.initials: I
authors.lastname: Spriet
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002956:Citrulline / Q000097:blood; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007413:Intestinal Mucosa; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000097:blood* / Q000139:chemically induced; D009181:Mycoses / Q000517:prevention & control; D013535:Suspensions; D013607:Tablets; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D013535:Suspensions; D013607:Tablets; D014230:Triazoles; D002956:Citrulline; C101425:posaconazole
keywords: Allogeneic HSCT; Citrulline; Mucositis; Posaconazole oral suspension; Posaconazole tablet