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Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment

Poly (ADP-ribose) polymerase (PARP) inhibitors are small-molecule inhibitors of PARP enzymes (including PARP1, PARP2, and PARP3) that exhibit activity against tumor cells with defects in DNA repair. In recent years, five PARP inhibitors, olaparib, niraparib, rucaparib, talazoparib and veliparib, hav...

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Autores principales: Zhao, Dehua, Long, Xiaoqing, Wang, Jisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673935/
https://www.ncbi.nlm.nih.gov/pubmed/36405648
http://dx.doi.org/10.2147/DDDT.S387920
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author Zhao, Dehua
Long, Xiaoqing
Wang, Jisheng
author_facet Zhao, Dehua
Long, Xiaoqing
Wang, Jisheng
author_sort Zhao, Dehua
collection PubMed
description Poly (ADP-ribose) polymerase (PARP) inhibitors are small-molecule inhibitors of PARP enzymes (including PARP1, PARP2, and PARP3) that exhibit activity against tumor cells with defects in DNA repair. In recent years, five PARP inhibitors, olaparib, niraparib, rucaparib, talazoparib and veliparib, have been developed for the treatment of solid tumors, particularly in patients with breast-related cancer antigen (BRCA) 1/2 mutations, or those without a functional homologous recombination repair pathway. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. The five PARP inhibitors are eliminated primarily via the liver and kidneys, hepatic or renal impairment may significantly affect their pharmacokinetics (PK). Therefore, it is important to know the effects of hepatic or renal impairment on the PK and safety of PARP inhibitors. In this review, we characterize and summarize the effects of hepatic and renal function on the PK of PARP inhibitors and provide specific recommendations for clinicians when prescribing PARP inhibitors in patients with hepatic or renal impairment.
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spelling pubmed-96739352022-11-19 Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment Zhao, Dehua Long, Xiaoqing Wang, Jisheng Drug Des Devel Ther Review Poly (ADP-ribose) polymerase (PARP) inhibitors are small-molecule inhibitors of PARP enzymes (including PARP1, PARP2, and PARP3) that exhibit activity against tumor cells with defects in DNA repair. In recent years, five PARP inhibitors, olaparib, niraparib, rucaparib, talazoparib and veliparib, have been developed for the treatment of solid tumors, particularly in patients with breast-related cancer antigen (BRCA) 1/2 mutations, or those without a functional homologous recombination repair pathway. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. The five PARP inhibitors are eliminated primarily via the liver and kidneys, hepatic or renal impairment may significantly affect their pharmacokinetics (PK). Therefore, it is important to know the effects of hepatic or renal impairment on the PK and safety of PARP inhibitors. In this review, we characterize and summarize the effects of hepatic and renal function on the PK of PARP inhibitors and provide specific recommendations for clinicians when prescribing PARP inhibitors in patients with hepatic or renal impairment. Dove 2022-11-14 /pmc/articles/PMC9673935/ /pubmed/36405648 http://dx.doi.org/10.2147/DDDT.S387920 Text en © 2022 Zhao et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Zhao, Dehua
Long, Xiaoqing
Wang, Jisheng
Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title_full Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title_fullStr Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title_full_unstemmed Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title_short Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment
title_sort dose adjustment of poly (adp‑ribose) polymerase inhibitors in patients with hepatic or renal impairment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673935/
https://www.ncbi.nlm.nih.gov/pubmed/36405648
http://dx.doi.org/10.2147/DDDT.S387920
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