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.
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D005110:Extracellular Space; D005493:Folic Acid Antagonists; D007700:Kinetics; D008198:Lymph Nodes / Q000098:blood supply; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008727:Methotrexate / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D005493:Folic Acid Antagonists; D008727:Methotrexate