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Axitinib plasma pharmacokinetics and ethnic differences.
Ying Chen1, Akiyuki Suzuki, Michael A Tortorici
1Clinical Pharmacology, Pfizer Inc, 10555 Science Center Drive, San Diego, CA, 92121, USA.
Investigational New Drugs
|February 10, 2015
Summary
Axitinib pharmacokinetics and safety are similar in Asian and non-Asian populations. This study found no clinically significant ethnic differences, meaning dose adjustments for axitinib are not necessary based on ethnicity.
Area of Science:
- Pharmacology
- Oncology
- Clinical Research
Background:
- Axitinib is a tyrosine kinase inhibitor approved for advanced renal cell carcinoma.
- Ethnic variations in drug-metabolizing enzymes may affect axitinib pharmacokinetics.
- Regulatory approval in Asian countries requires ethnic-specific evaluations.
Purpose of the Study:
- To compare axitinib pharmacokinetics and pharmacodynamics in Asian and Caucasian populations.
- To evaluate the influence of ethnicity on axitinib metabolism and disposition.
- To determine if ethnicity-based dose adjustments for axitinib are warranted.
Main Methods:
- Pharmacokinetic analysis of oral axitinib in healthy Asian subjects and Asian patients with advanced solid tumors.
- Comparison of axitinib plasma concentrations and exposure between Asian and Caucasian cohorts.
- Pooled population pharmacokinetic analysis incorporating ethnic data.
Main Results:
- Axitinib exhibited similar pharmacokinetic profiles in Asian and non-Asian subjects.
- No clinically meaningful effect of ethnicity on axitinib disposition was observed.
- Pharmacodynamic properties of axitinib were not significantly influenced by ethnic factors.
Conclusions:
- Axitinib pharmacokinetics are not sensitive to ethnic factors.
- Ethnicity does not warrant dose adjustments for axitinib.
- The findings support the use of axitinib without ethnic-specific dosing modifications.
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