Within the blood vessel, the drug is transported mainly by convection with negligible reactions. Once extravasated into the tumour intersti tium, drug particles penetrate through the intersititum MEK162 msds via diffusion and convection and at the same time they may be taken up by tumour cells. The drug is treated as a blood borne solute and its transport is governed by a diffusion convection reaction equation. Solute dynamics in the blood vessel is governed by Where cv refers to drug concentration in the vascular space, and Dv is drug diffusivity in the vascular space. The boundary conditions are the surrounding host tissue nor functional lymphatics in the host tissue are explicitly described. However, it is possible to incorporate the effect of lymphatic drainage in the current set up by imposing a mixed boundary condition at the outer surface.

Simulations with both BCs gave essentially identical results for the stimuli used here. The effect of the host tissue will be explicitly examined in a future study. BC assigns an inward solute flux into the interstitium, which can be determined by the Kedem Katchalsky equation BC prescribes a pulse injection at the vessel inlet with a constant intensity S and infusion time T, in which Heaviside term H indicates infusion occurs during the period of t 0 to t T. BC defines a convective flux at the outlet. BC sets an outward solute flux across the leaky wall boundary. Solute dynamics in the interstitium is governed by the extracellular and intracellular drug transport.

Extracellular drug concentration Where P is drug diffusive permeability across the vessel wall, ��f is osmotic reflection coefficient, clm is the log mean concentration across the vessel wall, and JF is the fluid flux across the vessel wall, which is determined by Starlings law. Intracellular drug concentration The intracellular drug concentration depends on the cor responding extracellular drug concentration according to Where cE and cI refer to the extracellular and intracellular drug concentration, respectively, DE is diffusion coefficient transmembrane transport. This is given by of drug in the interstitium, while ct is tumour cell density. V1, V2, kE and kI are constants that describe transport across the cell membrane, in which V1 and V2 are the maximum rates of transmembrane transport, while k1 and k2 are the Michaelis Menten constants for transmembrane transport.

Anacetrapib Eqn. 9a describes diffusion, convection of extracellular selleck chemical Tofacitinib drugs and their uptake/pumping out by tumour cells with the last terms expressed by Michaelis Menten kinetics. The boundary conditions are BC describes a no flux condition at the other boundaries of the interstitium. In the current study, neither It is noted that drug binding to plasma proteins is neglected in the current study.