Doxil — The First FDA-Approved Nano-Drug: From an Idea to a Product - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 377

12.5 Doxil Performance in Humans

12.5.1 Pharmacokinetics and Passive Targeting to

Tumors

The data presented in Figure 12.8 are the first proof of passive
targeting due the EPR eff ect in humans (Gabizon et al., 1994a).
Doxorubicin when administered as Doxil show and high and
selective tumor localization as was first demonstrated in the our
“first in man Doxil” study, conducted by us in Jerusalem in 1991-1994
and published in Cancer Research in 1994 (Gabizon et al., 1994a).

Figure 12.8 Doxorubicin levels in patients' tumor biopsies, comparing free
doxorubicin and Doxil (from Gabizon et al., 1994a, 1995).

This pilot study, which includes 53 courses of Doxil (average three
per patient spaced 3 to 4 weeks apart) was aimed to characterize and
compare in cancer patients the pharmacokinetics and accumulation
of doxorubicin in malignant eff usions after administration of Doxil
or of free drug (DOX). It clearly demonstrated much higher levels of
doxorubicin both in cells and interstitial fluids of the tumor after Doxil
administration than after DOX administration. Using the cationic ion
exchanger Dowex-50 (Druckmann et al., 1989; Amselem et al., 1990),
we found that more than 98% of the plasma doxorubicin after Doxil