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Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients

Kim Vanstraelen1, Juergen Prattes2, Johan Maertens3

  • 1Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium. Kim_vanstraelen@hotmail.com.

European Journal of Clinical Pharmacology
|April 13, 2016
PubMed
Abstract

Insights

Posaconazole tablets are recommended over oral suspension for allogeneic hematopoietic stem cell transplant patients to ensure adequate drug exposure, especially when intestinal mucositis is present. This prevents low posaconazole plasma concentrations.

Area of Science:

  • Pharmacokinetics
  • Transplantation Medicine
  • Infectious Disease Prophylaxis

Background:

  • Low posaconazole plasma concentrations (PPCs) are common in allogeneic hematopoietic stem cell transplant (HSCT) patients, often due to impaired gastrointestinal absorption.
  • Intestinal mucositis, a common complication post-HSCT, can significantly affect drug bioavailability and therapeutic efficacy.

Purpose of the Study:

  • To investigate the impact of intestinal mucositis severity on posaconazole exposure in allogeneic HSCT patients.
  • To compare the pharmacokinetic profiles of posaconazole oral suspension and tablets in the context of mucositis.

Main Methods:

  • A prospective pharmacokinetic study involving allogeneic HSCT patients receiving posaconazole prophylaxis.
  • Measurement of steady-state posaconazole plasma concentrations (PPCs) using high-performance liquid chromatography.
  • Assessment of intestinal mucositis severity via plasma citrulline levels, a biomarker for enterocyte mass.

Main Results:

  • Posaconazole oral suspension yielded lower PPCs in HSCT patients with higher citrulline levels (indicating mucositis) compared to those with lower citrulline levels.
  • Posaconazole tablets maintained higher PPCs irrespective of citrulline levels, suggesting less impact from mucositis.
  • Hematological patients without HSCT showed higher PPCs with the oral suspension compared to HSCT patients.

Conclusions:

  • Posaconazole tablets are preferable to the oral suspension for HSCT patients, particularly during the immediate post-transplant period.
  • Using posaconazole tablets can help mitigate the risk of insufficient drug exposure caused by intestinal mucositis in HSCT recipients.
Keywords:
Allogeneic HSCTCitrullineMucositisPosaconazole oral suspensionPosaconazole tablet

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