Methotrexate bioavailability

Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 61):S27-32. Epub 2010 Oct 28.


The clinical relevance of the concept of bioavailability rests on two main principles. First, that measurement of the active component at the site of action is generally not possible and, secondly, that a relationship exists between on the one hand efficacy and/or safety and on the other hand concentration of the active compound or its active metabolite(s) in the systemic circulation. Applying these principles to the current knowledge on methotrexate (MTX), it is clear that bioavailability of MTX is an important parameter for optimal dosing. In this manuscript the current knowledge on MTX bioavailability is reviewed. This review reveals that bioavailability of MTX in higher oral doses is decreased, most probably by limitation of absorption from the gastro-intestinal tract. It is suggested that higher doses can be given either by splitting the oral dose or by parenteral administration. Both will result in improved bioavailability as compared with one higher oral dose. However, larger, prospective studies directly comparing the efficacy and safety of the splitted oral dose strategy and the switch to parenteral MTX are needed.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics*
  • Biological Availability
  • Drug Administration Routes
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Drug Interactions
  • Humans
  • Intestinal Absorption
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / analogs & derivatives
  • Methotrexate / pharmacokinetics*
  • Polyglutamic Acid / analogs & derivatives
  • Polyglutamic Acid / pharmacokinetics


  • Antirheumatic Agents
  • Polyglutamic Acid
  • methotrexate polyglutamate
  • Methotrexate