In vivo methotrexate transport in murine Lewis lung tumor

J Pharm Sci. 1979 Aug;68(8):941-5. doi: 10.1002/jps.2600680806.

Abstract

Methotrexate uptake by murine Lewis lung tumor was measured in vivo over a wide dose range. The data were analyzed according to a model previously developed for tissues in which methotrexate uptake is rate limited by transport across the cell membrane. Methotrexate transport in this tumor followed Michaelis-Menten kinetics with a rate constant for permeability (k/K) of 0.012 min-1. The methotrexate binding capacity of dihydrofolate reductase in the tumor was not exceeded at any dose studied. A low membrane permeability in conjunction with a high dihydrofolate reductase level explains the resistance of this tumor to methotrexate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Membrane Permeability
  • Dose-Response Relationship, Drug
  • Lung Neoplasms / metabolism*
  • Male
  • Methotrexate / blood
  • Methotrexate / metabolism*
  • Mice
  • Models, Biological
  • Neoplasms, Experimental / metabolism
  • Tetrahydrofolate Dehydrogenase / metabolism
  • Time Factors

Substances

  • Tetrahydrofolate Dehydrogenase
  • Methotrexate