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March 1986

Division of Physician-Provider Time Between Ambulatory and In-Bed Patients in the Various Medical Specialties-Reply

Author Affiliations

Durham. NC

Arch Intern Med. 1986;146(3):603. doi:10.1001/archinte.1986.00360150257035

As the cornerstone of anti-rheumatic therapy in rheumatoid arthritis, high doses of salicylates are frequently employed in combination with methotrexate sodium. Maier and colleagues correctly emphasize the potential clinical importance of interaction between these two drugs. Salicylates may increase serum methotrexate levels by either reducing glomerular filtration or interfering with tubular secretion of methotrexate as Maier and his co-workers explain. Although therapeutic salicylate levels decrease methotrexate binding to serum protein by 20% to 60%, displacement of protein-bound methotrexate by a salicylate probably results in only slight increases in free methotrexate concentration.1 For displacement from binding sites to be significant, a drug must be greater than 90% bound, and its volume of distribution should not exceed extracellular water.2 In the case of methotrexate, only about 60% is protein-bound, and the free drug rapidly distributes into total body water.1

Whether increased or sustained methotrexate serum levels contribute to

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