Pharmacokinetics of amphotericin B colloidal dispersion in liver failure

Introduction

Clinical studies on the elimination of amphotericin B (AMB) lipid formulations in liver failure have been lacking so far. Therefore, the pharmacokinetics of AMB colloidal dispersion (ABCD) was assessed in critically ill patients with cholestatic liver failure.

Patients and methods

Time-concentration profiles were determined in critically ill patients with cholestatic liver failure and in critically ill patients with normal hepatic function requiring ABCD for invasive fungal infections. Lipid-associated and liberated AMB were separated by solid phase extraction and quantified by high performance liquid chromatography.

Results

Three patients with impaired and two patients with normal hepatic function (one patient on day 1, one patient on day 5 of therapy) were enrolled so far. After a single dose of ABCD, the AMB half life was similar in patients with impaired and normal liver function. The AMB clearance was slower in liver failure (0.15 vs. 0.54 L/h/kg for total AMB, 0.22 vs. 0.55 L/h/kg for the liberated AMB fraction and 0.52 vs. 35.6 L/kg for lipid-associated AMB) and the apparent volume of distribution was smaller (2.2 vs. 10.9 L/kg for total AMB, 3.1 vs. 11.2 L/kg for liberated and 8.2 vs. 154.5 L/h/kg for lipid-associated AMB).

Conclusion

The elimination of ABCD appears to be delayed in cholestatic liver failure. More pharmacokinetic data are required to establish reliable dose recommendations for ABCD in patients with liver failure.