Interspecies scaling of regional drug delivery.

Calculation of the pharmacokinetic advantage of regional drug administration requires knowledge of the relevant intercompartment transport parameter. In a lumped model this is the blood (or plasma) flow rate for intra-arterial drug infusion or the permeability-area product for intraperitoneal or intrathecal administration. It is suggested that the perfusion of many tissues and the intrinsic permeability of the peritoneal surface or the brain-cerebrospinal fluid interface are similar among mammals. This provides a clear allometric basis for interspecies scaling based on organ size or surface areas. Intra-arterial or intrathecal treatment of the brain or meninges is a particularly interesting problem because of the relatively large brain of humans and because increased folding results in a cortical surface area that is almost proportional to brain size. Major unresolved issues remain concerning the distributed character of the processes such as streaming of drug infused into an artery and nonuniform mixing of cerebrospinal fluid.