Vol 52, No 6 (2021)
Original research article
Published online: 2021-11-08

open access

Page views 6273
Article views/downloads 1257
Get Citation

Connect on Social Media

Connect on Social Media

Therapeutic drug monitoring of posaconazole for effective prophylaxis of invasive fungal infections in pediatric patients: a pilot study

Karolina Liszka1, Matylda Resztak2, Paulina Zalewska2, Krzysztof Kałwak1
Acta Haematol Pol 2021;52(6):578-583.

Abstract

Introduction: Posaconazole, a second-generation triazole agent, is a drug with wide interindividual variation in bioavailability and variability of pharmacokinetics. The European Conference on Infections in Leukemia recommends the implementation of posaconazole therapeutic drug monitoring (TDM) in children to provide certainty regarding the efficacy of treatment and to increase its safety. A concentration of posaconazole in plasma in prophylactic regimens of above 0.7 mg/L is recommended.

The aim of our pilot study was to discover the most effective method of posaconazole plasma concentration measurement, and to analyze posaconazole pharmacokinetics profiles in pediatric patients on posaconazole prophylaxis.

Material and methods: Children receiving oncological treatment or hematopoietic stem cell transplantation in the Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology in Wroclaw Medical University Hospital were included in the trial. Posaconazole concentration was determined at the MonitLabTM laboratory using a newly validated high-performance liquid chromatography with fluorescence detector method.

Results: Initial analysis shows that the major problem in patients on antifungal prophylaxis is inadequately low plasma drug concentration.

Conclusions: Clinical trials on TDM of posaconazole should be developed.

Article available in PDF format

View PDF Download PDF file

References

  1. Groll AH, Pana D, Lanternier F, et al. 8th European Conference on Infections in Leukaemia. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021; 22(6): e254–e269.
  2. Chen Lu, Krekels EHJ, Verweij PE, et al. Pharmacokinetics and pharmacodynamics of posaconazole. Drugs. 2020; 80(7): 671–695.
  3. Dzierżanowska-Fangrat K, Gil L, Jakubas B, et al. Recommendations for therapy of invasive fungal disease in patients with hematological malignancy or undergoing hematopoietic stem cell transplantation. Post Nauk Med. 2015; 28(6): 411–418.
  4. Welzen MEB, Brüggemann RJM, Van Den Berg JM, et al. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease. Pediatr Infect Dis J. 2011; 30(9): 794–797.
  5. Cendejas-Bueno E, Forastiero A, Rodriguez-Tudela JL, et al. HPLC/UV or bioassay: two valid methods for posaconazole quantification in human serum samples. Clin Microbiol Infect. 2012; 18(12): 1229–1235.
  6. Wissen CP, Burger DM, Verweij PE, et al. Simultaneous determination of the azoles voriconazole, posaconazole, isavuconazole, itraconazole and its metabolite hydroxy-itraconazole in human plasma by reversed phase ultra-performance liquid chromatography with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2012; 887–888: 79–84.
  7. Chhun S, Rey E, Tran A, et al. Simultaneous quantification of voriconazole and posaconazole in human plasma by high-performance liquid chromatography with ultra-violet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 852(1-2): 223–228.
  8. Kahle K, Langmann P, Schirmer D, et al. Simultaneous determination of voriconazole and posaconazole concentrations in human plasma by high-performance liquid chromatography. Antimicrob Agents Chemother. 2009; 53(7): 3140–3142.
  9. Tang P. Determination of posaconazole in plasma/serum by high-performance liquid chromatography with fluorescence detection. Separations. 2017; 4(2): 16.
  10. Müller C, Arndt M, Queckenberg C, et al. HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases. Mycoses. 2006; 49 Suppl 1: 17–22.
  11. Buckner SL, Ceesay MM, Pagliuca A, et al. Measurement of posaconazole, itraconazole, and hydroxyitraconazole in plasma/serum by high-performance liquid chromatography with fluorescence detection. Ther Drug Monit. 2011; 33(6): 735–741.
  12. Alffenaar JWC, Wessels AMA, van Hateren K, et al. Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878(1): 39–44.
  13. Jenkins N, Black M, Schneider HG. Simultaneous determination of voriconazole, posaconazole, itraconazole and hydroxy-itraconazole in human plasma using LCMS/MS. Clin Biochem. 2018; 53: 110–115.
  14. Chae H, Cho SY, Yu H, et al. Determination of posaconazole concentration with LC-MS/MS in adult patients with hematologic malignancy. Clin Chim Acta. 2015; 450: 220–226.
  15. Vogeser M, Rieger C, Ostermann H, et al. A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med. 2009; 47(5): 579–584.
  16. Rochat B, Pascual A, Pesse B, et al. Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing. Antimicrob Agents Chemother. 2010; 54(12): 5074–5081.
  17. Störzinger D, Swoboda S, Lichtenstern C, et al. Development and validation of a high-performance liquid chromatography assay for posaconazole utilizing solid-phase extraction. Clin Chem Lab Med. 2008; 46(12): 1747–1751.
  18. Groll AH, Castagnola E, Cesaro S, et al. Fourth European Conference on Infections in Leukaemia, Infectious Diseases Working Party of the European Group for Blood Marrow Transplantation (EBMT-IDWP), Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC-IDG), International Immunocompromised Host Society (ICHS), European Leukaemia Net (ELN). Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014; 15(8): e327–e340.
  19. Gil L, Kałwak K, Piekarska A, et al. Antifungal management in adults and children with hematological malignancies or undergoing hematopoietic cell transplantation: recommendations of Polish Society of Hematology and Blood Transfusion, Polish Society of Pediatric Oncology and Hematology, and Polish Adult Leukemia Study Group, 2020. Acta Haematol Pol. 2020; 51(2): 60–72.