Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China

Fangyi Li; Minggen Zhou; Zheng Jiao; Zijun Zou; Erqian Yu; Zhijie He

doi:10.1016/j.jgar.2021.03.011

Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China

J Glob Antimicrob Resist. 2021 Jun:25:238-263. doi: 10.1016/j.jgar.2021.03.011. Epub 2021 Apr 15.

Authors

Fangyi Li¹, Minggen Zhou¹, Zheng Jiao², Zijun Zou¹, Erqian Yu³, Zhijie He⁴

Affiliations

¹ Department of Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang West Road, Guangzhou 510120, Guangdong, China.
² Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: jiaozhen@online.sh.cn.
³ Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang West Road, Guangzhou 510120, Guangdong, China. Electronic address: hezhijie@mail.sysu.edu.cn.

PMID: 33845162
DOI: 10.1016/j.jgar.2021.03.011

Abstract

Objectives: Effective antifungal therapy is important to reduce mortality in patients with invasive fungal infections (IFIs). Numerous factors affect pharmacokinetic/pharmacodynamic (PK/PD) parameters in critically-ill patients. To guide individualised administration in critically-ill patients, it is of great significance to determine the population pharmacokinetics of caspofungin.

Methods: A prospective study in 42 ICU patients with IFIs was conducted in China. A population pharmacokinetic model of caspofungin was established using a non-linear mixed-effects model, which was utilised to investigate the effects of demographic indices, liver function and kidney function on pharmacokinetics. Additionally, appropriate dosages of caspofungin under various scenarios were determined based on MICs and probability of target attainment (PTA) at specific dosages.

Results: In critically-ill Chinese patients, clearance (CL), volume of distribution (V) and area under the curve at steady-state (AUC_ss) of caspofungin were 0.32 L/h, 6.77 L and 135.47 mg•h/L, respectively. Blood albumin and total bilirubin levels were factors affecting CL, while body weight was the only factor affecting V among Chinese people with relatively low weight compared with other populations. A maintenance dose of 50 mg caspofungin achieved a high PTA for treating IFIs caused by Candida albicans (MIC ≤ 0.06 mg/L) and Candida glabrata (MIC ≤ 0.125 mg/L). The maintenance dose of caspofungin should be adjusted to 70-200 mg for IFIs caused by C. albicans (MIC, 0.06-0.125 mg/L). For IFIs caused by Candida parapsilosis, an MIC > 0.03 mg/L is associated with a very low PTA, but higher doses of caspofungin or alternative antifungals need to be further studied.

Conclusion: The population pharmacokinetic model established here described well the PK/PD characteristics of caspofungin in critically-ill Chinese patients. These results could guide the formulation of individualised caspofungin dosing regimens for critically-ill patients.

Keywords: Caspofungin; China; ICU; Intensive care unit; Invasive fungal infection; Pharmacokinetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caspofungin
China
Humans
Intensive Care Units*
Probability
Prospective Studies

Substances

Caspofungin