Stereoselective Interaction of Trimethoprim-Sulfamethoxazole with the Separated Enantiomorphs of Racemic Warfarin in Man

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Abstract
IN a previous study of the interaction between racemic warfarin (a mixture of the levorotatory and dextrorotatory enantiomorphs) and trimethoprim–sulfamethoxazole (TMP-SMZ) in man, marked augmentation of hypoprothrombinemia with little change in the plasma concentrations of warfarin was found.1 On the basis of those data, it was concluded that the interaction did not have a pharmacokinetic basis. However, other drugs, such as phenylbutazone, have a diametrically opposite pharmacokinetic effect on each enantiomorph of warfarin.2 To determine whether the interaction between racemic warfarin and TMP-SMZ is stereoselective and could have a concealed pharmacokinetic basis, the experiments were repeated with the separated enantiomorphs . . .