Trial reportBritish journal of clinical pharmacology2016
Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment.
Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed.
- Updated Population Pharmacokinetic Model of Cabozantinib Integrating Various Cancer Types Including Hepatocellular Carcinoma.Journal of clinical pharmacology · 2019Trial
- Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Analysis.Journal of clinical pharmacology · 2018Trial
- Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses.Targeted oncology · 2017Trial
- A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis.Blood · 2017Trial
- Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma.British journal of haematology · 2017Trial
- Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment.British journal of clinical pharmacology · 2016Trial
- Organoboronic acids/esters as effective drug and prodrug candidates in cancer treatments: challenge and hope.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.Molecules (Basel, Switzerland) · 2023Article
- Review
- Population pharmacokinetic/pharmacodynamic joint modeling of ixazomib efficacy and safety using data from the pivotal phase III TOURMALINE-MM1 study in multiple myeloma patients.CPT: pharmacometrics & systems pharmacology · 2022Article
- Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle.International journal of molecular sciences · 2022Article
- Pharmacodynamics and pharmacokinetics of proteasome inhibitors for the treatment of multiple myeloma.Expert opinion on drug metabolism & toxicology · 2019Review
- Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.Clinical pharmacokinetics · 2019Review
- Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.Clinical pharmacology and therapeutics · 2019Review
- Next-generation proteasome inhibitors for cancer therapy.Translational research : the journal of laboratory and clinical medicine · 2018Review
- A phase I study to assess the mass balance, excretion, and pharmacokinetics of [Investigational new drugs · 2018Article
- How publication guidelines for clinical pharmacology trials may help to accelerate knowledge transfer.British journal of clinical pharmacology · 2018Article
- Progressive multifocal leukoencephalopathy during ixazomib-based chemotherapy.Current oncology (Toronto, Ont.) · 2018Article
- Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling.Clinical pharmacokinetics · 2017Article
- Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma.Targeted oncology · 2017Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim of the present study was to characterize the pharmacokinetics of the oral proteasome inhibitor, ixazomib, in patients with solid tumours and moderate or severe hepatic impairment, to provide posology recommendations.
methodsEligible adults with advanced malignancies for which no further effective therapy was available received a single dose of ixazomib on day 1 of the pharmacokinetic cycle; patients with normal hepatic function, moderate hepatic impairment or severe hepatic impairment received 4 mg, 2.3 mg or 1.5 mg, respectively. Blood samples for single-dose pharmacokinetic characterization were collected over 336 h postdose. After sampling, patients could continue to receive ixazomib on days 1, 8 and 15 in 28-day cycles.
resultsOf 48 enrolled patients (13, 15 and 20 in the normal, moderate and severe groups, respectively), 43 were pharmacokinetics-evaluable. Ixazomib was rapidly absorbed (median time to reach peak concentration was 0.95-1.5 h) and highly bound to plasma proteins, with a similar mean fraction bound (~99%) across the three groups. In patients with moderate/severe hepatic impairment (combined group), the geometric least squares mean ratios (90% confidence interval) for unbound and total dose-normalized area under the plasma concentration vs. time curve from time zero to the time of the last quantifiable concentration in reference to the normal hepatic function group were 1.27 (0.75, 2.16) and 1.20 (0.79, 1.82), respectively. Seven (15%) of the 48 patients experienced a grade 3 drug-related adverse event; there were no drug-related grade 4 adverse events.
conclusionsIn patients with moderate/severe hepatic impairment, unbound and total systemic exposures of ixazomib were 27% and 20% higher, respectively, vs. normal hepatic function. A reduced ixazomib starting dose of 3 mg is recommended for patients with moderate or severe hepatic impairment.
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