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

• Published in: The New England journal of medicine Vol. 302; no. 1; pp. 33 - 35
• Main Author: O'Reilly, Robert A
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 03.01.1980
• Subjects: Adult; Antibiotics; Anticoagulants; Case reports; Drug dosages; Drug Interactions; Experiments; Federal regulation; Humans; Male; Medical research; Prothrombin Time; Stereoisomerism; Structure-Activity Relationship; Sulfamethoxazole; Sulfamethoxazole - pharmacology; Trimethoprim; Trimethoprim - pharmacology; Trimethoprim-sulfamethoxazole; Warfarin; Warfarin - pharmacology
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198001033020106

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 . . .