title: Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA).
  
  
  METHODS
  A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic analysis was performed in each patient after oral and subcutaneous administration of the same dose of MTX. MTX serum concentrations were measured by a fluorescence polarization immunoassay. Pharmacokinetic analysis was performed with an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters.
  
  
  RESULTS
  The median MTX dose was 30 mg weekly (range 25-40 mg). A 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after oral MTX was 0.64 (range 0.21-0.96) compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 administration regimens.
  
  
  CONCLUSIONS
  Bioavailability of a higher oral dose of MTX in adult patients with RA is highly variable, and on average two-thirds that of the subcutaneous administration. To improve efficacy of MTX at dosages of 25 mg weekly or more, a change to parenteral administration should be considered.
authors.affiliation: Department of Rheumatology, Medisch Spectrum Twente, Enschede, The Netherlands. m.hoekstra@ziekenhuis-mst.nl
authors.forename: Monique
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Cees
authors.initials: C
authors.lastname: Haagsma
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.forename: Johannes
authors.initials: J
authors.lastname: Proost
authors.forename: Antonius
authors.initials: A
authors.lastname: Knuif
authors.forename: Mart
authors.initials: M
authors.lastname: van de Laar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate