Biliary elimination of low-dose methotrexate in humans.
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%).
Nuernberg
B
B
Department of Pharmacology and Toxicology, University of Erlangen-Nuernberg, West Germany.
Koehnke
R
R
Solsky
M
M
Hoffman
J
J
Furst
D E
DE
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged; D009994:Osmolar Concentration
C011864:7-hydroxymethotrexate; D008727:Methotrexate