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To the Editor: I read with interest the article by Hoekstra, et al on the bioavailability of higher doses of methotrexate (MTX)1. In the introduction the authors write that "pharmacokinetic studies in adult patients with rheumatoid arthritis (RA) show comparable bioavailability of oral and parenteral MTX in doses up to 25 mg weekly." However, most studies performed with doses ranging from 10 to 25 mg have shown a significantly reduced bioavailability of oral MTX compared with parenteral MTX. For example, in the study by Herman, et al2 the bioavailability of 10 mg oral MTX ranged from 25% to 100%, with a mean of 73%; in the study by Auvinet, et al3 the bioavailability of 15 mg oral MTX ranged from 45% to 80% (mean 60%); Oguey, et al4 found a mean absorption rate of 67% (range 28–94%) with 15 mg, and in the study by Korber5, administering 25 mg, the absorption rate was 73% (range 42–129%). These data show that the bioavailability of oral MTX also in doses less than 25 mg weekly is highly variable and significantly lower compared to parenteral administration. The clinical impression of incomplete resorption of oral MTX was the reason we started MTX treatment always by parenteral application in patients with RA: the parenteral route was used with relatively high doses of 25 or 15 mg to ensure the patient received an effective dose. Later, an oral dose sufficient for efficacy could be titrated. In patients with inadequate response to oral MTX, parenteral administration should be considered. ROLF RAU, MD, PhD, Department of Rheumatology, Evangelisches Fachkrankenhaus, Rosenstrasse 2, D-40882 Ratingen, Germany.
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 RA. J Rheumatol 2004;31:645-8. 2. Herman RA, van Pedersen P, Hoffman J, Furst DE. Pharmacokinetics of low dose methotrexate in rheumatoid arthritis patients. J Pharm Sci 1989;78:165-71. 3. Auvinet B, Jarrier I, Le-Levier F, Pegon Y, Turcant A, Allain P. Comparative bioavailability of methotrexate given orally or intramuscularly in rheumatoid arthritis [letter]. Presse Med 1992;21:822. 4. Oguey D, Kolliker F, Gerber NJ, Reichen J. Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1992;35:611-4. 5. Korber H, Iven H, Gross WL. Bioavailability and pharmacokinetics of methotrexate and its metabolite 7-hydroxy-MTX after low dose MTX (25 mg) in patients with chronic rheumatiod diseases [abstract]. Arthritis Rheum 1992;Suppl 35:S142.
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