Pharmacokinetic drug evaluation of ixazomib citrate for the treatment of multiple myeloma

Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):91-99. doi: 10.1080/17425255.2018.1417388. Epub 2017 Dec 19.

Abstract

multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients. In this paper, we focus on its pharmacokinetics features, as well as its safety and efficacy in clinical studies. Expert opinion: ixazomib can be considered an oral analogue of bortezomib, with 9.5-day half-life, 58% of oral bioavailability, and a large distribution volume of 543L. These features make it a versatile molecule, potentially useful both in combination and as single agent. Oral route of administration and good efficacy/safety profile are its winning characteristics, providing the rationale for a future role also in the maintenance setting.

Keywords: Ixazomib; maintenance therapy; multiple myeloma; pharmacokinetics; proteasome inhibitors.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Biological Availability
  • Boron Compounds / administration & dosage*
  • Boron Compounds / adverse effects
  • Boron Compounds / pharmacokinetics
  • Dexamethasone / administration & dosage
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / pharmacokinetics
  • Half-Life
  • Humans
  • Lenalidomide
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / pharmacokinetics
  • Salvage Therapy
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Tissue Distribution

Substances

  • Boron Compounds
  • Protease Inhibitors
  • Thalidomide
  • ixazomib
  • Dexamethasone
  • Lenalidomide
  • Glycine