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Abstract

Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.

Monique Hoekstra, Cees Haagsma, Cees Neef, Johannes Proost, Antonius Knuif and Mart van de Laar
The Journal of Rheumatology April 2004, 31 (4) 645-648;
Monique Hoekstra
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Cees Haagsma
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Cees Neef
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Johannes Proost
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Antonius Knuif
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Mart van de Laar
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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. 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.

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The Journal of Rheumatology
Vol. 31, Issue 4
1 Apr 2004
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Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.
Monique Hoekstra, Cees Haagsma, Cees Neef, Johannes Proost, Antonius Knuif, Mart van de Laar
The Journal of Rheumatology Apr 2004, 31 (4) 645-648;

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Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis.
Monique Hoekstra, Cees Haagsma, Cees Neef, Johannes Proost, Antonius Knuif, Mart van de Laar
The Journal of Rheumatology Apr 2004, 31 (4) 645-648;
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