The kinetics of methotrexate distribution in spontaneous canine lymphosarcoma
- 1 April 1975
- journal article
- Published by Springer Science and Business Media LLC in Journal of Pharmacokinetics and Biopharmaceutics
- Vol. 3 (2), 77-97
- https://doi.org/10.1007/bf01066017
Abstract
A mathematical model is presented to simulate the time-dependent uptake of methotrexate in spontaneous canine lymphosarcomas in vivo.Blood flow rates 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, with the maximum facilitated transport ranging from 0.002 to 0.007 μg/min/ml for the separate tumors studied and a Michaelis constant for transport equal to 0.2 μg/ml. This is in the range of Michaelis constants reported for normal tissues in rats in vivoand in several cell lines in vitro.Keywords
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