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To the Editor: We thank Dr. Rau for his comment on our article1. Indeed, there have been different studies comparing bioavailability of oral and parenteral methotrexate (MTX) in doses up to 25 mg weekly in patients with rheumatoid arthritis (RA). The mean relative bioavailability (F) of the studies comparing oral and subcutaneous or intramuscular routes of administration of MTX, in the dose range of 5 to 25 mg weekly, range from 0.85 to 1.0, more or less comparable. Dr. Rau is right when he states there are strong interindividual differences that always have to be taken into account. The studies mentioned by Dr. Rau compare intravenous and oral MTX, and they show a reduced bioavailability of oral MTX (range mean F 0.6–0.73). The question is whether the 3 parenteral routes of administration are strictly comparable concerning bioavailability. Seideman, et al's study2 in 8 patients with RA treated with 15 mg MTX did show this, but other studies in RA are lacking. We agree with Dr. Rau that, even in the lower dose ranges, you have take a reduced and variable bioavailability into account. The treatment of patients with RA is very much individually determined. Given the data on the bioavailability of MTX and the dose effect relation of oral MTX in doses up to 25 mg weekly, in the lower dose ranges, MTX can well be administered orally. With insufficient response a parenteral route of administration can be considered. The "splitting" of the oral dose may also be an alternative strategy to improve bioavailability, as was observed in our patients with RA taking MTX doses of 25 mg weekly or more (unpublished data). MONIQUE HOEKSTRA, MD, Department of Rheumatology, Medisch Spectrum Twente, Enschede, The Netherlands. REFERENCES 1. Hoekstra M, Haagsma C, Neef C, Proost J, Knuif A, van de Laar M. Bioavailability of higher dose MTX comparing oral and subcutaneous administration in patients with rheumatoid arthritis. J Rheumatol 2004;31:645-8. 2. Seideman P, Beck O, Eksborg S, Wenneberg M. The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumatoid arthritis. Br J Clin Pharmacol 1993;35:409-12. |
