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

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. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.