Pharmacokinetic and therapeutic consequences of liposomal drug delivery: Fluorodeoxyuridine and Amphotericin B as examples

Liposome encapsulation can affect the pharmacokinetic behavior and therapeutic effects on the both polar and non polar drugs. We have examined the effects of liposome encapsulation on the clearance and metabolism of the water soluble anti tumor agent fluorodeoxyuridine, finding a reduced rate of clearance, increased tissue retention and alteration of metabolic processing. We have also examined the effect of encapsulation of Amphotericin B, a lipid soluble antibiotic, on the therapeutic effects of this agent against candida albicans infection in mice. Encapsulation of Amphotericin B markedly reduces its toxicity, including nephrotoxicity, while causing minimal changes in its therapeutic potency. Thus it is possible to administer larger doses of encapsulated than free drug and to obtain superior therapeutic action.