Interstitial infusion, direct

DRUG MODALITY II DELIVERY FROM A POINT SOURCE — DIRECT INTERSTITIAL INFUSION... 

FIGURE 9.8 Schematic drawing of direct interstitial infusion showing a 32-gauge infusion cannula placed in the center of the rat caudate nude us—p u ta in en. 

Case Study 3 ChemopalUdectomy in Patients with Parkinson s Disease Using Direct Interstitial Infusion... 

Direct interstitial infusion has been applied to the treatment of patients with advanced Parkinson s disease, and the design of the protocol is instructive (29). Motor control is severely compromised in these patients because degradation of the substantia nigra ultimately results in massive overinhibition of the motor cortex by the globus pallidus interna (Gpi). One therapeutic approach is to thermally ablate a portion of the Gpi to reduce this inhibition and restore freedom of movement. However, thermal ablation also risks destroying the optic nerve that forms the floor of the Gpi structure. Hence, a chemical means of destroying the Gpi has been evaluated as a potentially more selective alternative. 

Controlled chemical destruction of the Gpi is possible using direct interstitial infusion of the exci-totoxin quinolinic acid (pyridine dicarboxylate MW 167). The property of quinolinic acid that makes it attractive for this purpose is its ability to selectively... 

The general principles underlying distributed kinetic models of drug delivery by transfer across tissue interfaces (intraperitoneal and intraventricular delivery) and by direct interstitial infusion (low- and high-flow microinfusion) have been presented and... 

Morrison PF. A computational model of direct interstitial infusion of macromolecules into the spinal cord. Ann Biomed Eng 2003 31 448-61. 

Morrison PF. Direct interstitial infusion of NKl targeted neurotoxin into the spinal cord A computational model. Am. J. Physiol. 2003 285 R243-54. 

Anti-tumor activity of bevacizumab has been reported in various preclinical animal models (primary and metastatic) with a broad array of tumor types [106, 107]. Clinical studies have further validated the focal role of VEGF in cancer. A single infusion of bevacizumab at 5 mg/kg in patients with primary and locally advanced adenocarcinoma of the rectum demonstrated direct and rapid antivascular effect in human tumors, with decreases in tumor perfusion, vascular volume, microvascular density, and interstitial pressure [108]. Clinical efficacy of bevacizumab in combination with 5-FU- and irinotecan-based regimens has been demonstrated in patients with metastatic colorectal cancer a significant improvement in overall survival time was observed compared with chemotherapy alone (20.3 versus 15.6 months for chemotherapy plus bevacizumab versus chemotherapy alone) [109]. 

When bulk fluid flow is present (v 0), concentration profiles can be predicted from Equation 10-17, subject to the same boundary and initial conditions. This set of equations has been used to describe concentration profiles during micro-infusion of drugs into the brain [33]. In addition to Equation 10-17, conservation equations for water are needed to determine the variation of fluid velocity in the radial direction. Relative concentrations are predicted by assuming that the brain behaves as a porous medium (i.e., velocity is related to pressure gradient by Darcy s law, see Equation 6-9). Water introduced into the brain can expand the interstitial space this effect is balanced by the flow of water in the radial direction away from the infusion source and, to a lesser extent, by the movement of water across the capillary wall. 

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