Biliary elimination of low-dose methotrexate in humans

Arthritis Rheum. 1990 Jun;33(6):898-902. doi: 10.1002/art.1780330620.


We studied the pharmacokinetics of methotrexate (MTX) in a 64-year-old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokinetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre- and post-cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half-lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary elimination of MTX (8.7-26.0%) and its principal 7-hydroxy metabolite (1.5-4.6%).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / urine
  • Bile / metabolism*
  • Biological Availability
  • Drug Administration Schedule
  • Humans
  • Male
  • Methotrexate / analogs & derivatives
  • Methotrexate / blood
  • Methotrexate / pharmacokinetics*
  • Methotrexate / urine
  • Middle Aged
  • Osmolar Concentration


  • 7-hydroxymethotrexate
  • Methotrexate