Population Pharmacokinetics of Capivasertib in Patients with Advanced or Metastatic Solid Tumours
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View abstract on PubMed
Summary
This summary is machine-generated.This study developed a population pharmacokinetic model for capivasertib, a pan-AKT inhibitor. Most patient factors did not significantly impact capivasertib pharmacokinetics, suggesting no dose adjustments are needed.
Area Of Science
- Pharmacology
- Oncology
- Clinical Pharmacology
Background
- The PI3K/AKT pathway is frequently overactivated in various cancers.
- Capivasertib is a potent and selective inhibitor targeting the pan-AKT pathway.
Purpose Of The Study
- To develop a population pharmacokinetic (PK) model for capivasertib.
- To evaluate the influence of intrinsic and extrinsic factors on capivasertib PK.
Main Methods
- Combined pharmacokinetic data from four Phase I/II studies.
- Assessed covariates including dose, schedule, patient demographics, organ function, and concomitant medications.
- Utilized a three-compartment model to describe capivasertib disposition.
Main Results
- Capivasertib PK showed moderate time- and dose-dependent clearance.
- Body weight, paclitaxel co-administration, food effect, and formulation significantly impacted PK, but effects were <20%.
- Most assessed covariates, including age, sex, race, and renal/hepatic function, did not significantly affect capivasertib PK.
Conclusions
- Capivasertib PK exhibits moderate between-subject variability.
- Identified factors like body weight and paclitaxel co-administration have statistically significant but low impact on exposure.
- No a priori dose adjustments are necessary for intrinsic and extrinsic factors based on this population PK analysis.
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