External evaluation of published population pharmacokinetic models of posaconazole

Autor: Shuqi Huang, Qin Ding, Nan Yang, Zexu Sun, Qian Cheng, Wei Liu, Yejun Li, Xin Chen, Cuifang Wu, Qi Pei
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2022.1005348
Popis: Population pharmacokinetic (PopPK) models of posaconazole have been established to promote the precision dosing. However, the performance of these models extrapolated to other centers has not been evaluated. This study aimed to conduct an external evaluation of published posaconazole PopPK models to evaluate their predictive performance. Posaconazole PopPK models screened from the PubMed and MEDLINE databases were evaluated using an external dataset of 213 trough concentration samples collected from 97 patients. Their predictive performance was evaluated by prediction-based diagnosis (prediction error), simulation-based diagnosis (visual predictive check), and Bayesian forecasting. In addition, external cohorts with and without proton pump inhibitor were used to evaluate the models respectively. Ten models suitable for the external dataset were finally included into the study. In prediction-based diagnostics, none of the models met pre-determined criteria for predictive indexes. Only M4, M6, and M10 demonstrated favorable simulations in visual predictive check. The prediction performance of M5, M7, M8, and M9 evaluated using the cohort without proton pump inhibitor showed a significant improvement compared to that evaluated using the whole cohort. Consistent with our expectations, Bayesian forecasting significantly improved the predictive per-formance of the models with two or three prior observations. In general, the applicability of these published posaconazole PopPK models extrapolated to our center was unsatisfactory. Prospective studies combined with therapeutic drug monitoring are needed to establish a PopPK model for posaconazole in the Chinese population to promote individualized dosing.
Databáze: Directory of Open Access Journals