Biliary elimination of low‐dose methotrexate in humans

Publisher Website
Google Scholar
Abstract
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%).