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Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin

Authors :
Nuo Xu
Yufei Shi
Yixue Wang
Wenyao Mak
Wenyu Yang
Kar Weng Ng
Yue Wu
Zhijia Tang
Qingfeng He
Gangfeng Yan
Xiaoqiang Xiang
Xiao Zhu
Source :
Pharmaceutics, Vol 16, Iss 6, p 819 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Background: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. Objective: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. Methods: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. Results: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. Conclusion: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.

Details

Language :
English
ISSN :
19994923
Volume :
16
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.bf6ebeaa7c4e4fc68a5843de4c6596cb
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics16060819