PT  - JOURNAL ARTICLE
AU  - Monique Hoekstra
AU  - Cees Haagsma
AU  - Cees Neef
AU  - Johannes Proost
AU  - Antonius Knuif
AU  - Mart van de Laar
TI  - Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.
DP  - 2004 Apr 01
TA  - The Journal of Rheumatology
PG  - 645--648
VI  - 31
IP  - 4
4099  - http://www.jrheum.org/content/31/4/645.short
4100  - http://www.jrheum.org/content/31/4/645.full
SO  - J Rheumatol2004 Apr 01; 31
AB  - 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. CONCLUSION: 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.