Establishment and validation of population pharmacokinetic model of docetaxel in malignant tumor patients
- VernacularTitle:恶性肿瘤患者多西他赛群体药动学模型的建立及验证
- Author:
Junping WANG
1
;
Zhengyu WU
1
;
Zhixia LOU
2
;
Yuan YAO
1
;
Tingting WU
1
;
Zongtao HU
2
Author Information
1. Center of Pharmacy，Hefei Cancer Hospital，Chinese Academy of Sciences，Hefei 230031，China
2. Abdominal Oncology Center，Hefei Cancer Hospital，Chinese Academy of Sciences，Hefei 230031，China
- Publication Type:Journal Article
- Keywords:
docetaxel;
blood concentration;
population pharmacokinetic model;
malignant tumor
- From:
China Pharmacy
2022;33(18):2261-2265
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To establis h and validate a population pharmacokinetic model of docetaxel in malignant tumor patients. METHODS The clinical data of malignant tumor patients treated with chemotherapy regimen containing docetaxel in our hospital from June 2019 to December 2021 were retrospectively collected . According to the results of blood concentration detection ， based on the three -compartment model the nonlinear mixed effect model （NONMEM）was used ；covariates（age，weight，height， body surface area ，Karnofsky performance scale ，total protein ，albumin，total bilirubin ，aspartate aminotransferase ，alanine aminotransferase and serum creatinine ）affecting clearance （CL）were screened by “forward inclusion and backward exclusion ”； the population pharmacokinetic model of docetaxel was established . The model was tested for goodness -of-fit diagnosis and internal validation by Bootstrap . RESULTS A total of 264 measured blood concentrations of 132 patients with malignant tumors during chemotherapy were included . The covariates that had significant effect on CL of docetaxel were serum creatinine and total bilirubin （P＜0.01）. The results of Bootstrap analysis （parameter median values and 95% confidence intervals ）were close to predict results of the established model ；the final model estimated that the population typical value of docetaxel CL was 37.82 L/h. CONCLUSIONS The population pharmacokinetic model of docetaxel in malignant tumor patients is established successfully ， which can be used for the formulation and optimization of clinical individualized regimen .
