Toxicological studies of plafibride. Part 4: Interaction of plafibride with other drugs

The possible pharmacological interaction was studied between N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) and a series of products with analgesic, anticoagulant, antidepressant, antidiabetic, Beta-blocking, diuretic, hypotensive, nootropic, tranquillizing and vasodilator activities. In the experiment the LD50 of each product was compared with that found for the joint administration of the product and plafibride. Plafibride increased the acute toxicity of reserpine and potentiated its hypothermic effect in the mouse; it did not alter its effect on arterial pressure in dog and rat nor its effect on palpebral ptosis in the mouse. Although plafibride did not potentiate the acute toxicity of warfarin, its anticoagulant activity was potentiated, possibly due to the movement of warfarin from its binding sites to the plasma proteins.