title: Mixing during intravertebral arterial infusions in an in vitro model.
abstract: Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments.
authors.affiliation: Division of Bioengineering and Physical Science, National Institutes of Health, Bethesda, MD 20892-5766, USA. rjlutz@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lutz
authors.forename: Kathy
authors.initials: K
authors.lastname: Warren
authors.forename: Frank
authors.initials: F
authors.lastname: Balis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Patronas
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dedrick
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D003388:Cranial Fossa, Posterior; D006801:Humans; D007261:Infusions, Intra-Arterial; D008955:Models, Cardiovascular; D014711:Vertebral Artery
chemical_list: D000970:Antineoplastic Agents