The kinetics of methotrexate distribution in spontaneous canine lymphosarcoma

A mathematical model is presented to simulate the time-dependent uptake of methotrexate in spontaneous canine lymphosarcomas in vivo. Blood flow ratew in these tumors are high so that transport to the tumor is limited by cell membrane resistance. A significant amount of rapidly exchangeable methotrexate appears to exist in extracellular space loosely bound to proteins or cell membranes. Transmembrane drug transport follows Michaelis-Menten kinetics, wigh the maximum facilitated transport ranging from 0.002 to 0.007 mug/min/ml for the separate tumors studied and a Michaelis constant for transport equal to 0.2 mug/ml. This is in the range of Michaelis constants reported for normal tissues in rats in vivo and in several cell linnes in vitro.