Pharmacokinetics of high molecular weight agents.

The various high molecular weight agents discussed in this chapter are at different stages of gestation, but as yet none have had a clear clinical impact despite many years of scientific effort. The problems that have been encountered along the way for many agents are similar: how to avoid reticuloendothelial trapping and how to achieve adequate penetration of a macromolecule into a solid tumour. The solutions offered to these problems are as diverse as the agents themselves, and, as a spin-off, our understanding of tumour cell behaviour (eg endocytosis) has improved. For many of the systems discussed, it remains unclear whether this approach is just a complex way of administering a continuous low dose infusion of the cytotoxic component. Advances in this field appear to have accelerated over the last 2-3 years, and it should not be much longer before these scientifically pleasing and elegant systems are shown to have clinical advantages over conventional cytotoxic drug delivery.