Establishment and validation of a population pharmacokinetic model for apatinib in patients with tumors
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View abstract on PubMed
Summary
This summary is machine-generated.This study developed a population pharmacokinetic model for apatinib in Chinese cancer patients. Apatinib clearance is influenced by liver function (aspartate aminotransferase) and co-administered drugs, suggesting potential dose adjustments for optimal treatment.
Area Of Science
- Pharmacokinetics and Pharmacodynamics
- Oncology Drug Development
- Clinical Pharmacology
Background
- Apatinib is an oral anti-cancer medication used in China.
- Understanding its pharmacokinetic variability is crucial for optimizing patient outcomes.
- Population pharmacokinetic (PPK) modeling is a valuable tool for characterizing drug disposition in diverse patient populations.
Purpose Of The Study
- To develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients.
- To identify key covariates influencing apatinib pharmacokinetics, specifically its clearance (CL/F).
- To provide a basis for potential dose individualization strategies.
Main Methods
- Collected 199 plasma concentration data points from 91 Chinese oncology patients treated with oral apatinib.
- Utilized nonlinear mixed-effects modeling (NONMEM) to develop the PPK model.
- Assessed covariates including age, gender, body weight, liver function (AST), renal function, and co-administered drugs.
- Validated the model using bootstrap and normalized prediction distribution error (NPDE) methods.
Main Results
- A one-compartment model with first-order elimination best described apatinib pharmacokinetics.
- Aspartate aminotransferase (AST) levels and co-administered drug type significantly impacted apatinib CL/F.
- The model provided specific equations for CL/F based on AST and drug combinations (monoclonal antibodies, paclitaxel, other chemotherapy, or monotherapy).
Conclusions
- A robust PPK model for apatinib was successfully established in Chinese oncology patients.
- Liver function (AST) and co-medication are critical factors influencing apatinib CL/F.
- These findings highlight the need for personalized dosing strategies, especially when apatinib is used with different chemotherapy regimens.
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