1. Background Caspofungin is an echinocandin antifungal agent licensed as a first-line therapy for invasive candidiasis in patients with moderate to severe illness or recent exposure to azoles [1]. Caspofungin acts by inhibiting the synthesis of (1,3)-β-D-glucan of the fungal cell wall, ultimately causing cell death [2]. The recommended dosage regimen of caspofungin is a loading dose of 70 mg followed by 50 mg daily (70/50 mg), administered intravenously over 1 h. Caspofungin is highly protein bound (~ 96%) and metabolizes slowly in the liver [3-5]. Its liver uptake is a biphasic process and its binding to the surface of hepatocytes is fast and reversible. One study demonstrated that the uptake of caspofungin by liver is related to the active organic anion transporting polypeptide 1B1 (OATP1B1) [6]. Caspofungin plasma clearance is 10 to 12 ml/min [3] and eliminated mainly by hepatic, for only one to two percent of it is cleared renal [7]. The elimination of caspofungin from plasma is …show more content…
and determine whether the different dosage regimens of caspofungin could achieved PK/PD targets in the general patient populations, ICU and HI patients. A MCS was performed using the simulated data of WB-PBPK model. Through virtual simulation of Gastroplus, we obtained the AUC of different dosage regimens of these special patients. The MCS methods, the pharmacodynamic targets for Candida species (fAUC0-24/MIC ratio for C. albicans, C. glabrata and C. parapsilosis) and the minimum inhibitory concentration distributions for Candida species have been described previously [31]. The optimal dosage regimens were evaluated to compare the simulated probabilityof target attainment (PTA) and cumulative fraction ofresponse (CFR) in these subjects. A CFR value of ≥ 90% was considered to be an appropriate empirical dosage regimen, as previously established by the OPTAMA