Tetracyclines plasma protein binding

Some lists, reviews and books on interactions say that chloramphenicol, aminosalieylie aeid, sodium salieylate, sulfamethoxypyridazine, tetracycline or tolbutamide interact with methotrexate, apparently based largely on the preliminary findings of a study in which male mice were treated for 5 days with each of 4 doses of methotrexate (1.53 to 12.25 mg/kg intravenously) and immediately afterwards with non-toxic intraperitoneal doses of the drugs listed. These drugs were said to decrease the lethal dose and/or decrease the survival time of the mice That is to say, the toxicity of the methotrexate was increased. The reasons are not understood, but it is suggested that displacement of the methotrexate from its plasma protein binding sites could result in a rise in the levels of unbound and active methotrexate, and in the case of sodium salicylate to a decrease in renal clearance. 

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