COMPARATIVE PHARMACOKINETICS, DISTRIBUTIONS IN TISSUE, AND INTERACTIONS WITH BLOOD PROTEINS OF CONVENTIONAL AND STERICALLY STABILIZED LIPOSOMES CONTAINING 2',3'-DIDEOXYINOSINE

The pharmacokinetics and distribution in tissue of 2',3'-dideoxyinosin e (ddI) encapsulated in sterically stabilized liposomes have been eval uated in rats. Most of the sterically stabilized liposomes concentrate d in the spleen with a peak level at 24 h after their intravenous inje ction. An extended half-life in plasma was observed for sterically sta bilized liposomes (14.5 h) compared with that of conventional liposome s (3.9 h). The systemic clearance of ddI incorporated in sterically st abilized liposomes was 180 times lower than that of the free drug. The levels of in vitro and in vivo protein binding on both conventional a nd sterically stabilized liposomes were also evaluated. Results sugges t that the amount of proteins associated with liposomes might not be t he only factor involved in the in vivo clearance of liposomes, as this process may also be influenced by the nature of the bound blood prote ins.