Pharmacokinetic Models of Convection-Enhanced Drug Delivery

Abstract

Abstract Convection-enhanced delivery (CED) is a direct infusion technique that bypasses the blood–brain barrier and provides controlled, large-volume coverage. This local delivery method is one of few methods available for delivering macromolecular agents to central nervous tissues, since intraparenchymal infusions drive extracellular (interstitial) flows that overcome slow diffusion limits. Pharmacokinetic models that account for spatial and temporal distributions within targeted tissues during and after CED are useful tools in the design of drug trials. In this chapter, we summarize major parameters needed to quantify pharmacokinetics and we review three representative cases for distribution of: (i) a small-molecular–weight compound (quinolinic acid) in the brain, (ii) a macromolecular biologic (substance P-diphtheria toxin) within a three-dimensional model of the spinal cord, and (iii) a macromolecule (GDNF) to gray matter regions considering variations in catheter geometry.