A Systematic Review of the Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Ganciclovir/Valganciclovir in Allogeneic Haematopoietic Stem Cell Transplant Patients.

Autor: Selby PR; School of Medicine, University of Adelaide, Adelaide, SA, Australia. Philip.Selby@sa.gov.au.; Pharmacy Department, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000, Australia. Philip.Selby@sa.gov.au., Shakib S; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia., Peake SL; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, SA, Australia., Warner MS; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; Infectious Diseases Unit, The Queen Elizabeth Hospital, Adelaide, SA, Australia.; SA Pathology, Adelaide, SA, Australia., Yeung D; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; SA Pathology, Adelaide, SA, Australia.; Haematology Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia., Hahn U; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; SA Pathology, Adelaide, SA, Australia.; Haematology Unit, Royal Adelaide Hospital, Adelaide, SA, Australia., Roberts JA; Faculty of Medicine and Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, St Lucia, QLD, Australia.; Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
Jazyk: angličtina
Zdroj: Clinical pharmacokinetics [Clin Pharmacokinet] 2021 Jun; Vol. 60 (6), pp. 727-739. Date of Electronic Publication: 2021 Jan 30.
DOI: 10.1007/s40262-020-00982-z
Abstrakt: Background: Ganciclovir (GCV) and valganciclovir (VGCV) are the first-line agents used to prevent and treat cytomegalovirus (CMV) infection in allogeneic haematopoietic stem cell transplant (alloHCT) patients.
Objective: The aim of this work was to describe available data for the clinical pharmacokinetics, pharmacodynamics and toxicodynamics of GCV and VGCV and the potential of a therapeutic drug monitoring strategy to improve outcomes in the alloHCT population.
Methods: We systematically reviewed the pharmacokinetics (dose-exposure), pharmacodynamics (exposure-efficacy) and toxicodynamics (exposure-toxicity) of GCV and VGCV in alloHCT patients with CMV infection. Studies including alloHCT patients treated for CMV infection reporting the pharmacokinetics, pharmacodynamics and toxicodynamics of GCV or VGCV were searched for using the PUBMED and EMBASE databases from 1946 to 2019. Only studies involving participants > 12 years of age and available in the English language were included.
Results: A total of 179 patients were included in the 14 studies that met the inclusion criteria, of which 6 examined GCV pharmacokinetics only, while 8 also examined GCV pharmacodynamics and toxicodynamics. Reported pharmacokinetic parameters showed considerable interpatient variability and were different from other populations, such as solid organ transplant and human immunodeficiency virus-infected patients. Only one study found a correlation between neutropenia and elevated peak and trough GCV concentrations, with no other significant pharmacodynamic and toxicodynamic relationships identified. While therapeutic drug monitoring of GCV is performed in some institutions, no association between GCV therapeutic drug monitoring and clinical outcomes was identified.
Conclusion: Further studies of the pharmacokinetics, pharmacodynamics and toxicodynamics of GCV/VGCV in alloHCT patients are required to identify a more robust therapeutic range and to subsequently quantify the potential value of therapeutic drug monitoring of GCV/VGCV in the alloHCT population.
Databáze: MEDLINE
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