ArticleBritish journal of clinical pharmacology2018
Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inter-ethnic differences in pharmacokinetics-is there more that unites than divides?Pharmacology research & perspectives · 2021Pooled it
- Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor.Neuro-oncology · 2023Trial
- Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies.Journal of clinical pharmacology · 2022Trial
- Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.Clinical and translational science · 2021Trial
- Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism.eLife · 2025Article
- Asia-Inclusive Clinical Research and Development Enabled by Translational Science and Quantitative Clinical Pharmacology: Toward a Culture That Challenges the Status Quo.Clinical pharmacology and therapeutics · 2023Article
- Phase 1 study of alisertib (MLN8237) and weekly irinotecan in adults with advanced solid tumors.Cancer chemotherapy and pharmacology · 2021Article
- Biotransformation Pathways and Metabolite Profiles of Oral [Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Emerging serine-threonine kinase inhibitors for treating ovarian cancer.Expert opinion on emerging drugs · 2019Article
- Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.British journal of clinical pharmacology · 2018Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThis population pharmacokinetic analysis was conducted to describe quantitatively the regional differences and sources of interpatient variability on the apparent oral clearance of alisertib.
methodsA population pharmacokinetic analysis was performed on data from 671 cancer patients in Western countries and in Japan/East Asia to whom alisertib 5-150 mg once or twice daily (b.i.d.) was administered in multiple dosing schedules. The final model was used to simulate alisertib pharmacokinetics in patients in the West and East Asian regions in the single-agent schedule of 7 days of dosing in a 21-day cycle. Exposure-safety relationships for mechanism-related antiproliferative toxicities (neutropenia, mucositis and diarrhoea) were estimated by logistic regression.
resultsAlisertib pharmacokinetics were described by a two-compartment model with four-transit compartment absorption and linear elimination. The final model included a covariate effect of region on relative bioavailability, with patients in the East Asian region estimated to have a 52% higher bioavailability compared with Western patients. Population simulated exposure at 30 mg b.i.d. in patients in Asia was similar to that at 50 mg b.i.d. in Western patients [geometric mean (coefficient of variation) steady state area under the concentration-time curve over the dosing interval (AUC
conclusionsModel-based simulations support the achievement of similar alisertib exposures in patients in Asia who are administered a 40% lower dose compared with the Western population, thereby providing a quantitative clinical pharmacology bridging and regional dosing rationale for global drug development.
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