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Biotech / Medical : Cell Therapeutics (CTIC) -- Ignore unavailable to you. Want to Upgrade?

To: former_pgs who wrote (459)	2/24/2005 2:02:36 PM
From: quidditch	Respond to of 946

Thank you. That is clear, and makes more sense to me if the excretion of unmetabolized xyotax occurs in a short period of time. quid

To: former_pgs who wrote (459)	2/24/2005 2:34:56 PM
From: scaram(o)uche	Respond to of 946

>> a somewhat restricted diffusion mechanism << one big passive bag? if there's only two routes out of the can (obviously, we're not talking perfect here, neutropenia was anticipated from day 0), isn't it simplistic to assume that pissing at the tumor would be superior?......... Ann Biomed Eng. 2003 Feb;31(2):181-94. Related Articles, Links A model of fluid flow in solid tumors. Pozrikidis C, Farrow DA. Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA. cpozrikidis@ucsd.edu Solid tumors consist of a porous interstitium and a neoplastic vasculature composed of a network of capillaries with highly permeable walls. Blood flows across the vasculature from the arterial entrance point to the venous exit point, and enters the tumor by convective and diffusive extravasation through the permeable capillary walls. In this paper, an integrated theoretical model of the flow through the tumor is developed. The flow through the interstitium is described by Darcy's law for an isotropic porous medium, the flow along the capillaries is described by Poiseuille's law, and the extravasation flux is described by Starling's law involving the pressure on either side of the capillaries. Given the arterial, the venous, and the ambient pressure, the problem is formulated in terms of a coupled system of integral and differential equations for the vascular and interstitial pressures. The overall hydrodynamics is described in terms of hydraulic conductivity coefficients for the arterial and venous flow rates whose functional form provides an explanation for the singular behavior of the vascular resistance observed in experiments. Numerical solutions are computed for an idealized case where the vasculature is modeled as a single tube, and charts of the hydraulic conductivities are presented for a broad range of tissue and capillary wall conductivities. The results in the physiological range of conditions are found to be in good agreement with laboratory observations. It is shown that the assumption of uniform interstitial pressure is not generally appropriate, and predictions of the extravasation rate based on it may carry a significant amount of error.

To: former_pgs who wrote (459)	2/24/2005 3:18:46 PM
From: CrazyPete	Read Replies (2) \| Respond to of 946

> If 75% of the dose of Xyotax excreted unchanged, that means > that you only have 25% of the remaining dose to reach that > threshold and elicit the therapeutic effect. I disagree with your logic. You're begging the question of whether the premise of conjugated taxol derivatives is valid. It seems to me that there are lots of variables here: (1) rates of transport of the drug to tumor and other tissues; (2) rates of clearance of the drug and its metabolites by excretory pathways; and (3) rates of metabolism of the original drug in the tumor and other tissues. You're saying you don't believe that Xyotax can be so specifically targeted to tumor tissue. But small changes in the rates of any of these steps can cause large changes in steady-state concentrations of the active drug metabolites in the tumor, and large changes in how the drug is excreted. The excretion of Xyotax is dominated by kinetics in tissues that are very different from the tumor, so I think you really can't conclude much from this one data point.