A Systematic Review of the Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Ganciclovir/Valganciclovir in Allogeneic Haematopoietic Stem Cell Transplant Patients
Autor: | Philip Roland Selby, Sandra L. Peake, David T Yeung, Sepehr Shakib, Jason A. Roberts, Morgyn S. Warner, Uwe Hahn |
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Rok vydání: | 2021 |
Předmět: |
Pharmacology
Oncology Ganciclovir medicine.medical_specialty education.field_of_study Toxicodynamics medicine.diagnostic_test business.industry viruses Population Valganciclovir 03 medical and health sciences 0302 clinical medicine Therapeutic index Pharmacokinetics Therapeutic drug monitoring 030220 oncology & carcinogenesis Internal medicine Pharmacodynamics medicine Pharmacology (medical) education business 030215 immunology medicine.drug |
Zdroj: | Clinical Pharmacokinetics. 60:727-739 |
ISSN: | 1179-1926 0312-5963 |
Popis: | 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. 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. 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. 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. 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: | OpenAIRE |
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