Validation of the population pharmacokinetic model of docetaxel in breast cancer patients

ObjectiveTo explore the applicability of different docetaxel population pharmacokinetic(PPK) models in domestic breast cancer population, so as to provide a basis for establishing a suitable PPK model for domestic breast cancer patients.

MethodsThe literatures of docetaxel PPK model in PubMed, Embase, Web of Science, CNKI, and WanFang databases were searched by computer, the basic information of literature was extracted, the blood concentration data of docetaxel in domestic breast cancer patients were collected and fitted using Phoenix nonlinear mixed-effects model software.The fitting effects of blood drug concentration in breast cancer patients were analyzed using the diagnostic graph of observed concentration-predicted concentration of model fitting and visual predictve checks.

ResultsA total of 108 blood drug concentration data in 39 breast cancer patients were collected as external validation data sets to verify the docetaxel PPK model.Finally, 6 literatures were included in the study.The results of the established PPK model fitting found that LAUNAY-ILIADIS model had the best fitting effects(-2LL=933.34, AIC=993.34), followed by BRUNO model(-2LL=945.13, AIC=1 007.13), and the other models had the poor fitting effects.

ConclusionThe blood concentration data of docetaxel in the treatment of breast cancer in China do not fit well with the PPK model of docetaxel reported in most literatures.In order to study the pharmacokinetic characteristics of docetaxel for domestic breast cancer patients, it is necessary to establish a multi-center and large-sample PPK model for domestic breast cancer patients.