Identification of desethyl procainamide in patients: a new metabolite of procainamide.
Desethyl procainamide (PADE) was identified in the urine of a patient treated with procainamide (PA) by high-performance liquid chromatography followed by solid-probe mass spectrometry. PADE prevented ventricular fibrillation in chloroform-asphyxiated mice but PA was 1.5 times more potent than PADE with respect to dose and 1.7 times more potent with respect to plasma concentration measured after administration of antiarrhythmic ED50 doses of the two compounds. N-acetylprocainamide was found to be 1.8 times more potent than desethyl N-acetylprocainamide with respect to dose and 2.9 times more potent with respect to plasma concentration. Measurements of PA, PADE, N-acetylprocainamide and desethyl-N-acetylprocainamide concentrations in 10 patients receiving long-term PA therapy suggest that only PA and N-acetylprocainamide concentrations make important contributions to observed therapeutic responses.
D000120:Acecainide / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D011342:Procainamide / Q000031:analogs & derivatives* / Q000378:metabolism*; D012119:Respiration; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; C028492:desethyl-N-acetylprocainamide; C028493:desethylprocainamide; D000120:Acecainide; D011342:Procainamide