Population pharmacokinetics of sirolimus in pediatric patients with kaposiform hemangioendothelioma: A retrospective study
- Dongdong Wang
- Xiao Chen
- Zhiping Li
Published online on: July 4, 2019
Copyright: © Wang et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
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Numerous studies have established population pharmacokinetics (PPK) models of sirolimus in various populations. However, a PPK model of sirolimus in Chinese patients with pediatric kaposiform hemangioendothelioma (PKHE) has yet to be established; therefore, this was the purpose of the present study. The present study was a retrospective analysis that utilized the trough concentration data obtained from traditional therapeutic drug monitoring‑based dose adjustments. A total of 17 Chinese patients with PKHE from a real‑world study were characterized by non‑linear mixed‑effects modeling. The impact of demographic features, biological characteristics and concomitant medications was assessed. The developed final model was evaluated via bootstrap and a prediction‑corrected visual predictive check. A one‑compartment model with first‑order absorption and elimination was used for modeling of data for PKHE. The typical values of apparent oral clearance (CL/F) and apparent volume of distribution (V/F) in the final model were 3.19 l/h and 165 liters, respectively. Age, alanine transaminase levels and sex were included as significant covariates for CL/F, while the duration of treatment with sirolimus was a significant covariate for V/F. In conclusion, the present study developed and validated the first sirolimus PPK model for Chinese patients with PKHE.