Caspofungin weight-based dosing supported by a population pharmacokinetic model in critically ill patients.

The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per one dosing occasion. Fifteen patients with (suspected) invasive candidasis had one dosing occasion and five had two dosing occasions measured on day 3 (±1) of treatment. Pmetrics was used for population pharmacokinetic modelling and probability of target attainment (PTA). A target 24-hour AUC value of 98 mg*h/L was used as an efficacy parameter. Secondarily the AUC/MIC targets of 450, 865 and 1185 were used to calculate PTAs for C. glabrata, C. albicans and C. parapsilosis respectively. The final 2-compartment model included weight as a covariate on volume of distribution (Vd). The mean Vd of the central compartment was 7.71 (SD 2.70) L/kg, the mean Ke was 0.09 (SD 0.04) h-1, the kcp was 0.44 (SD 0.39) h-1, and the kpc was 0.46 (SD 0.35) h-1 A loading dose of 2 mg/kg on the first day, followed by 1.25 mg/kg as a maintenance dose was chosen. With this dose, 98% of the patients were expected to reach the AUC target on the first day and 100% of the patients on the third day. The registered caspofungin dose might not be suitable for all overweight (≥120 kg), over 80% of average weight (78 kg), and around 25% of lower weight (≤50 kg) critically ill patients. A weight-based dose regimen might be appropriate for achieving adequate exposure of caspofungin in ICU patients. PMID: 326609...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research