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1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir?
BACKGROUND: Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug re...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809420/ http://dx.doi.org/10.1093/ofid/ofz360.1402 |
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author | Martson, Anne-Grete Sturkenboom, Marieke G G Berger, Stefan P Damman, Kevin Verschuuren, Erik A M Blokzijl, Hans Bakker, Martijn Span, Lambert F R Touw, Daan J van der Werf, Tjip S Knoester, Marjolein Alffenaar, Jan-Willem C |
author_facet | Martson, Anne-Grete Sturkenboom, Marieke G G Berger, Stefan P Damman, Kevin Verschuuren, Erik A M Blokzijl, Hans Bakker, Martijn Span, Lambert F R Touw, Daan J van der Werf, Tjip S Knoester, Marjolein Alffenaar, Jan-Willem C |
author_sort | Martson, Anne-Grete |
collection | PubMed |
description | BACKGROUND: Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug resistance, which can both lead to treatment failure. Therapeutic drug monitoring (TDM) is a good tool to estimate drug exposure in these patients. With this observational study we aimed to evaluate which patients would benefit most from TDM. METHODS: An observational study was performed in adult solid-organ and stem cell transplant recipients on routine (val)ganciclovir (dosed according to renal function, weight and indication). As valganciclovir is a prodrug of ganciclovir, only the latter was measured. Ganciclovir trough (C(trough)) and peak (C(peak)) concentrations were measured with a validated LC-MS/MS assay. The target concentrations defined for the study were 1–2 mg/L and 2–4 mg/L for prophylaxis and treatment, respectively, and over 5 mg/L toxic. RESULTS: From June 2018 to April 2019, 66 patients were included. Within this timeframe, 236 C(trough) and 52 C(peak) were measured with median of 4 samples per patient. The median C(trough) was 1.1 mg/L and 2.3 mg/L for prophylaxis and treatment, respectively. Over 50% of the concentrations were out of the therapeutic window. The median creatinine for all measurements was 100 µmol/L. Observational analysis showed patients with kidney failure and on continuous renal replacement therapy (CVVH) had more concentrations measured out of the predefined range (Figures 1 and 2). For one individual with augmented renal clearance we observed significantly lower concentrations during routine dosing. 6 toxic concentrations were measured (5 subjects); creatinine concentrations ranged 71–527 µmol/L in these individuals. A preliminary linear-mixed model analysis did not show drug formulation, age or gender as a significant predictor for ganciclovir concentrations. CONCLUSION: We believe that patients with decreased renal function, on CVVH or showing changes in renal function might benefit from TDM to guide therapy. TDM of ganciclovir for patients without renal failure remains debatable. Further studies with specific patient groups are needed to confirm these results. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. |
format | Online Article Text |
id | pubmed-6809420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68094202019-10-28 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? Martson, Anne-Grete Sturkenboom, Marieke G G Berger, Stefan P Damman, Kevin Verschuuren, Erik A M Blokzijl, Hans Bakker, Martijn Span, Lambert F R Touw, Daan J van der Werf, Tjip S Knoester, Marjolein Alffenaar, Jan-Willem C Open Forum Infect Dis Abstracts BACKGROUND: Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug resistance, which can both lead to treatment failure. Therapeutic drug monitoring (TDM) is a good tool to estimate drug exposure in these patients. With this observational study we aimed to evaluate which patients would benefit most from TDM. METHODS: An observational study was performed in adult solid-organ and stem cell transplant recipients on routine (val)ganciclovir (dosed according to renal function, weight and indication). As valganciclovir is a prodrug of ganciclovir, only the latter was measured. Ganciclovir trough (C(trough)) and peak (C(peak)) concentrations were measured with a validated LC-MS/MS assay. The target concentrations defined for the study were 1–2 mg/L and 2–4 mg/L for prophylaxis and treatment, respectively, and over 5 mg/L toxic. RESULTS: From June 2018 to April 2019, 66 patients were included. Within this timeframe, 236 C(trough) and 52 C(peak) were measured with median of 4 samples per patient. The median C(trough) was 1.1 mg/L and 2.3 mg/L for prophylaxis and treatment, respectively. Over 50% of the concentrations were out of the therapeutic window. The median creatinine for all measurements was 100 µmol/L. Observational analysis showed patients with kidney failure and on continuous renal replacement therapy (CVVH) had more concentrations measured out of the predefined range (Figures 1 and 2). For one individual with augmented renal clearance we observed significantly lower concentrations during routine dosing. 6 toxic concentrations were measured (5 subjects); creatinine concentrations ranged 71–527 µmol/L in these individuals. A preliminary linear-mixed model analysis did not show drug formulation, age or gender as a significant predictor for ganciclovir concentrations. CONCLUSION: We believe that patients with decreased renal function, on CVVH or showing changes in renal function might benefit from TDM to guide therapy. TDM of ganciclovir for patients without renal failure remains debatable. Further studies with specific patient groups are needed to confirm these results. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6809420/ http://dx.doi.org/10.1093/ofid/ofz360.1402 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Abstracts Martson, Anne-Grete Sturkenboom, Marieke G G Berger, Stefan P Damman, Kevin Verschuuren, Erik A M Blokzijl, Hans Bakker, Martijn Span, Lambert F R Touw, Daan J van der Werf, Tjip S Knoester, Marjolein Alffenaar, Jan-Willem C 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title | 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title_full | 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title_fullStr | 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title_full_unstemmed | 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title_short | 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir? |
title_sort | 1538. who will benefit from therapeutic drug monitoring of ganciclovir? |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809420/ http://dx.doi.org/10.1093/ofid/ofz360.1402 |
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