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Caspofungin PK in critically ill patients after the first and fourth doses: suggestions for therapeutic drug monitoring?
- Source :
- Journal of Chemotherapy; April 2020, Vol. 32 Issue: 3 p124-131, 8p
- Publication Year :
- 2020
-
Abstract
- We describe caspofungin pharmacokinetics (PK) after the first and fourth doses in 20 critically ill septic patients. Monte Carlo simulation was used to analyze the probability of target attainment (PTA) (AUC/MIC > 865) for Candidaspp. Caspofungin concentrations were analyzed by HPLC in plasma and urine. A great variability in PK parameters was observed after both doses. Patients were divided in two groups according to their AUC values (AUC ≤ 75 mg h/L cut-off). In the low-AUC group Cmax, Cmin and AUC were lower, while Vd and Cl were higher than in the high-AUC group (p < 0.05, both at day 1 and 4). The mean 24-h urinary recovery of the drug was 8 ± 6.3% (day1) and 9.8 ± 6.3 (day4). Monte Carlo simulation analysis (0.03–1 mg/L MIC-range) showed that PTA was guaranteed only for MICs ≤ 0.03 mg/L in the low-AUC group, and for MICs ≤ 0.06 mg/L in the high-AUC group. No group had a PTA ≥ 90% for 0.125 mg/L MIC (the epidemiological cut-off). Mortality was higher in low-AUC group (p < 0.01). In our ‘real-world’ population, no clinical data can predict which patient will have lower, suboptimal caspofungin exposure, therefore we suggest TDM to optimize caspofungin therapy and reduce the risk of selecting resistances (CEAVC, 32366/2015; OSS.15.114, NCT03798600).
Details
- Language :
- English
- ISSN :
- 1120009X and 19739478
- Volume :
- 32
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Journal of Chemotherapy
- Publication Type :
- Periodical
- Accession number :
- ejs53179274
- Full Text :
- https://doi.org/10.1080/1120009X.2020.1737783