PHARMACOKINETICS OF LONG-CIRCULATING LIPOSOMES

Association of drugs with carriers such as liposomes has marked effect s on both the pharmacokinetic profiles of the carrier and of the carri er-associated drug. In general, association of drugs with liposomes de lays drug absorption, alters and restricts drug biodistribution, decre ases the volume of distribution, delays clearance and retards drug met abolism. Surface modification of liposomes by the inclusion of hydroph ilic components (e.g., carbohydrates, glycolipids or polymers) to form long-circulating liposomes causes changes in the pharmacokinetic patt ern seen for unmodified (classical) liposomes. While classical liposom es have non-linear, saturable kinetics, long-circulating liposomes pos sess dose-independent, non-saturable, log-linear kinetics. The log-lin ear kinetics for long-circulating liposomes results from a significant decrease in the first phase of clearance into a high affinity, low ca pacity system, probably the cells of the mononuclear phagocyte system. An understanding of the pharmacokinetics of liposome-associated drugs is critical to the development of rationale strategies for therapeuti c applications of long-circulating liposomes.