Abstract
Preclinical and clinical investigation on proteasome as a druggable target in cancer has led to the development of proteasome inhibitors (PIs) with different pharmacodynamic and pharmacokinetic properties. For example, carfilzomib has a better safety profile and a lower risk of clinically relevant drug-drug interactions than bortezomib, whereas ixazomib can be orally administered on a weekly basis due to a very long elimination half-life and high systemic exposure. The purpose of this review article is to elucidate the quantitative and qualitative differences in potency, selectivity, pharmacokinetics, safety and drug-drug interactions of clinically validated PIs to provide useful information for their clinical use in real life setting.
Keywords:
Drug-drug interactions; Pharmacodynamics; Pharmacokinetics; Proteasome inhibitors; Safety.
Copyright © 2021 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Boron Compounds / adverse effects
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Boron Compounds / pharmacokinetics
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Boron Compounds / pharmacology
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Boron Compounds / therapeutic use
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Bortezomib / adverse effects
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Bortezomib / pharmacokinetics
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Bortezomib / pharmacology
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Bortezomib / therapeutic use
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Drug Interactions
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Glycine / adverse effects
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Glycine / analogs & derivatives
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Glycine / pharmacokinetics
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Glycine / pharmacology
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Glycine / therapeutic use
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Humans
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Multiple Myeloma / drug therapy
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Oligopeptides / adverse effects
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Oligopeptides / pharmacokinetics
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Oligopeptides / pharmacology
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Oligopeptides / therapeutic use
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Proteasome Inhibitors / adverse effects
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Proteasome Inhibitors / pharmacokinetics
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Proteasome Inhibitors / pharmacology
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Proteasome Inhibitors / therapeutic use*
Substances
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Antineoplastic Agents
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Boron Compounds
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Oligopeptides
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Proteasome Inhibitors
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Bortezomib
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ixazomib
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carfilzomib
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Glycine