Liposomal amphotericin B: a unique pharmacokinetic profile. An unfinished story.
Azanza JR, Barberán J.
José Ramón Azanza Perea, Servicio de Farmacología Clínica, Clínica Universidad de Navarra, Avenida Pío XII s/n - 31008 Pamplona, Spain
Amphotericin B in its lipid formulation continues to be the reference drug in the treatment of systemic fungal infections despite the time elapse since the development of this compound. The absence of fungal resistance, pharmacokinetics, and the better tolerability profile as compared with the remaining formulations of amphotericin B are sufficient reasons to justify its prominent therapeutic role.
The liposome containing liposomal amphotericin B is very stable in relation to the presence of cholesterol and phospholipids are not thermolabile, so that free amphotericin B is almost inexistent (<1%), which explains the reduced incidence of effects related to the drug administration, and a reduction in the incidence of nephrotoxicity (half than that with amphotericin B lipid complex) and that even in some studies at doses of 1 mg/kg has been shown to be negligible.
This profile explains the very high plasma drug concentrations and the reduced distribution volume and clearance, with a very prolonged elimination half-life. There are evidences showing that the liposome through amphotericin B is capable of binding to ergosterol present in the fungal membrane and only at this moment would be the antifungal released to exert its pharmacological effects.
CITATION Rev Esp Quimioter. 2012 Mar;25(1):17-24