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 .
ABSTRACT
This study aimed to evaluate the predictive performance of a vancomycin population pharmacokinetic model in 0-10 year Chinese pediatric patients. This study was approved by the Ethics Research Committee of the First Affiliated Hospital of Guangxi Medical University, data from hospitalized children ≤ 10 years of age who receiving vancomycin were collected retrospectively. Individual predictive values (IPRED) were estimated by Bayesian Analysis based on a previous published population pharmacokinetic model, and compared with the observed steady state trough concentration. As results, a total of 371 vancomycin serum concentrations from 191 patients were taken for the external validation. The mean error (ME), the mean relative prediction error (ME%), the mean absolute error (MAE) and the root mean square error (RMSE) in individual prediction method for the total patients were -0.50 mg·L-1, 6.03%, 1.84 mg·L-1, 2.86 mg·L-1 respectively. The correlation coefficient between individual predictions and detection values was 0.95. The stability and the predictive performance of model were accepted by goodness-of-fit, visual predictive check (VPC) and Bland-Altman. The percentage of individual prediction error within ± 30% was 82.75%. The above results suggest that, this Chinese pediatric population pharmacokinetic model in 0-10 years old has a good prediction performance. It can be applied to the design of initial treatment plan and predicting the extent of drug exposure.
ABSTRACT
Objective This study was designed to validate the utility of a population pharmacokinetic model established for vancomycin in patients with severe neurosurgical disease . Methods The clinical data including patient gender , age , body weight ,serum creatinine and albumin were collected retrospectively from patients in Nanjing Drum Tower Hospital to calculate the steady trough concentration of vancomycin using the previously established pharmacokinetic model .The predicted value was compared with the actual value .Results During the period from March 2013 to March 2014 ,53 blood samples with serum trough concentration of vancomycin were collected from 42 patients .The average trough concentration of vancomycin was 10 .9 mg/L (range from 1 .6 to 49 .1 mg/L) .The predicted trough level of vancomycin based on the population pharmacokinetic model was significantly correlated to the actual value(r=0 .857 ,P<0 .001) .The mean absolute percentage error was 0 .407 9 . The confidence interval was 9 .36‐14 .07 for the predicted values ,and 8 .92‐14 .32 for the actual values .Conclusions The pharmacokinetic model is valid and useful for planning intravenous dose of vancomycin in patients with severe neurosurgical disease .Large error (about 30% ) was observed in estimation of body weight due to coma .Reduced renal function following contrast agent and/or diuretic drug has an impact on the predicted results . The accuracy of prediction can be increased to nearly 70% after adjusting the covariates .