摘要

Caspofungin is a common treatment for fungal infections in intensive care unit (ICU) patients, and in these patients their pharmacokinetics are highly variable. So a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for measuring C-min in 18 ICU patients, and the exposure-response characteristics of caspofungin were investigated. The calibration curve included clinically relevant caspofungin concentrations, ranging from 0.05 to 20 mg L-1. The mean recovery rate ranged from 85.2% to 95.3%, while the intra-and interday precisions were < 5.5% and their accuracies were within the range of 96.2-102.3%. The overall C-min was 2.13 +/- 0.99 mg L-1 (mean +/- SD; range, 0.51-3.79 mg L-1). Patients were infected by either Candida spp. (n = 13) or Aspergillus spp. (n = 5), and caspofungin therapy was effective in 66.7% (n = 12) of them. 76.9% (10/13) patients (infected by Candida spp. and C-min > 1 mg L-1) achieved clinical success while 23.1% (3/13) patients (C-min > 1 mg L-1: n = 1; C-min < 1 mg L-1: n = 2) failed to show a clinical response. All five patients infected by Aspergillus spp. had a mean plasma C-min above 0.5 mg L-1, and only two achieved clinical success. Validated LC-MS/MS is a simple, rapid and accurate method that is suitable for monitoring the concentration of caspofungin. C-min exhibits a wide range in ICU patients, and relatively good treatment results are obtainable when C-min exceeds the 90% minimal inhibitory concentration (Candida spp: 1mg L-1; Aspergillus spp: 0.5 mg L-1).