title: Computational pharmacokinetic rationale for intra-arterial delivery to the brain.
abstract: Intra-arterial (IA) drug delivery has been proposed for the treatment of a wide range of brain diseases, including malignant brain tumors. However, pharmacokinetic optimization for IA drug delivery to the brain remains a challenge. In this report, we apply and expand the well-established Dedrick model of IA drug delivery to the brain and test the effects of modifying drug and delivery parameters. These simulations show that altering the properties of candidate drugs and physiological variables can have profound effects on regional deposition after IA injections. We show that drug and physiological optimization aimed at rapid drug extraction and sustained retention is necessary to maximize regional deposition after of IA injections.
authors.affiliation: Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
authors.forename: Johann N R
authors.initials: JN
authors.lastname: Cooke
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Ellis
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.|Institute for Computational Engineering and Sciences, University of Texas, Austin, TX, USA.
authors.forename: Shaolie
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Juliane
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.affiliation: Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA. sj121@cumc.columbia.edu.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D003198:Computer Simulation; D016503:Drug Delivery Systems; D006801:Humans; D007269:Injections, Intra-Arterial; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents
keywords: Blood-brain barrier; Brain tumor; Chemotherapy; Glioma