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Population Pharmacokinetics Model Repository for Caspofungin: a Systematic Review
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  • Nuo Xu,
  • Yufei Shi,
  • Yixue Wang,
  • Wen Yao Mak,
  • Yue Wu,
  • Wenyu Yang,
  • Zhijia Tang,
  • Qingfeng He,
  • Gangfeng Yan,
  • Xiaoqiang Xiang,
  • Xiao Zhu
Nuo Xu
Fudan University
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Yufei Shi
Fudan University School of Pharmacy
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Yixue Wang
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Wen Yao Mak
Hospital Pulau Pinang
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Yue Wu
Shenzhen Children's Hospital
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Wenyu Yang
Fudan University School of Pharmacy
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Zhijia Tang
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Qingfeng He
Fudan University School of Pharmacy
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Gangfeng Yan
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Xiaoqiang Xiang
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Xiao Zhu
School of Pharmacy, Fudan University, 201203, Shanghai, China.

Corresponding Author:[email protected]

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Caspofungin is an echinocandin antifungal commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis. Pharmacokinetic variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. We aimed to consolidate information from population pharmacokinetic studies, compare model performance, identify significant covariates affecting caspofungin’s PKs, evaluate probability of target attainment in different studies and assemble pharmacokinetic/pharmacodynamic target to address existing knowledge gaps that may warrant further investigation in future. We performed a systematic search strategy to review the PPK studies of caspofungin. Four databases were searched. We extracted information for the comparison of models, evaluation of the impact of covariates on clearance and apparent volume and the calculation of probability of target attainment under specific minimum inhibitory concentration. Thirteen studies were included. The simulation results showed that under labeled dose, pediatrics exhibited notably higher exposure than adults. Body size was the most identified covariate that affected both clearance and volume of distribution. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥ 90%. In contrast, for C. glabrata, 70% of the adult patients reached a PTA of ≥ 90%, while all pediatric patients achieved the same PTA level. At the recommended dosage, adults showed lower exposure to caspofungin compared to pediatrics. It is crucial to consider body size, liver function and serum albumin when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatrics.
26 Oct 2023Submitted to British Journal of Clinical Pharmacology
26 Oct 2023Assigned to Editor
26 Oct 2023Submission Checks Completed
26 Oct 2023Review(s) Completed, Editorial Evaluation Pending
06 Nov 2023Reviewer(s) Assigned