Pharmacokinetics of amphotericin B lipid complex in critically ill patients undergoing continuous venovenous haemodiafiltration

Abstract

The objective of this study was to examine the effect of continuous venovenous haemodiafiltration (CVVHDF) on the pharmacokinetics of amphotericin B (AmB) in critically ill patients following administration of amphotericin B lipid complex (ABLC). Plasma and ultrafiltrate (UF) samples were collected from patients administered ABLC and either receiving or not receiving CVVHDF. Pharmacokinetic (PK) analysis was performed on eight profiles from patients receiving CVVHDF and six profiles from patients not receiving CVVHDF. For patients receiving CVVHDF, the following median PK data were calculated: area under the concentration–time curve (AUC)=13.9h·μg/mL, volume of distribution at steady state (Vss)=1476L and drug clearance (CL)=27.4L/h; for patients not receiving CVVHDF, the corresponding median PK data were 11.5hμg/mL, 2048L and 43.7L/h, respectively. The median half-lives calculated during the dosage interval (t1/2int) were 30.9h and 32.5h on and off CVVHDF, respectively, and the total range of t1/2int values was 15.6–180.4h. Observed median peak concentrations on Day 1 were 0.563μg/mL and 0.468μg/mL in patients on and off CVVHDF, respectively. From AmB present in the UF, clearance via CVVHDF contributed<1% of total plasma clearance. The AmB concentration–time profiles for patients administered ABLC on and off CVVHDF were compared and no statistically significant differences in AUC, CL, t1/2int and Vss were observed. In conclusion, CVVHDF had no clinically significant effect on the pharmacokinetics of AmB following administration of ABLC.