Abstract

Objective

This study aimed to develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients and investigate the factors influencing the pharmacokinetics of apatinib.

Methods

We gathered 199 blood concentration monitoring data points from 91 inpatient oncology participants receiving oral apatinib at the Third Affiliated Hospital of Soochow University. Covariates, such as age, gender, body weight, and indices of liver and renal function, were examined to assess their influence on the pharmacokinetic parameters of apatinib. The PPK model was developed using the nonlinear mixed-effects modeling procedure (NONMEM), and model validation was conducted using the bootstrap method and normalized prediction distribution error (NPDE) method.

Results

The structural model adopted a one-compartment structure with first-order elimination. Notably, aspartate aminotransferase (AST) and the co-administered drug type emerged as primary covariates affecting apatinib clearance (CL/F). The finalized model was expressed as CL/F (L/h) = 56.7 × (AST/26.6)−0.298 × θ, when apatinib was combined with monoclonal antibodies, θ was 1; when combined with paclitaxel, θ was 0.58; when combined with other drugs (e.g., platinum, capecitabine, or the combination of tegafur, gimeracil, and oteracil potassium), θ was 1.60; When used as monotherapy, θ was 1.38. V/F = 674 L, and the absorption rate constant (Ka) was fixed at 0.08 h−1. Bootstrap results affirmed the model’s reliability and stability, while NPDE outcomes attested to the model’s fit.

Conclusion

Our study successfully established a PPK model for apatinib in oncology patients, revealing that liver function status and co-administered drug types significantly impacted apatinib CL/F. This finding underscored the potential necessity for dose adjustments to optimize efficacy, particularly in patients undergoing different chemotherapy regimens involving apatinib.

Details

Title
Establishment and validation of a population pharmacokinetic model for apatinib in patients with tumors
Author
Li’an Zuo; Ling, Jing; Hu, Nan; Chen, Rong
Pages
1-9
Section
Research
Publication year
2024
Publication date
2024
Publisher
BioMed Central
e-ISSN
14712407
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3126414877
Copyright
© 2024. This work is licensed under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.