The Relationship Between the Metabolism of Procainamide and Sulfamethazine

The metabolism of sulfamethazine (SMZ), which is acetylated by a bimodally distributed enzyme, and procainamide (PA) was compared in 21 normal volunteers, each given a single oral dose of SMZ and PA (10 mg/kg). Urinary PA and SMZ concentrations and acetylated metabolites, N-acetyl-procainamide (NAPA) and Ac-SMZ, were measured. Subjects with less than 64% Ac-SMZ in the 0–8 hour collection were termed “slow” and those with more than 64% were termed “fast” SMZ acetylators. Slow SMZ acetylators had 9.8 to 43.8% (24.1 ± 10.13) NAPA recovered, and fast SMZ acetylators, 22.0 to 42.6% (33.7 ± 7.29) NAPA, P < 0.01. In addition, the calculated half-life of PA metabolism for slow SMZ acetylators was 9.0 to 33.8 hours (18.4 ± 8.82) and for fast SMZ acetylators was 8.1 to 14.4 hours (10.9 ± 2.19), P < 0.01. For four subjects, SMZ acetylation phenotype did not correlate with the halflife of SMZ or PA metabolism; and in two, SMZ acetylation phenotype and half-life of metabolism did not correlate with the same PA indices. Even though slow SMZ acetylators have less NAPA recovered than fast SMZ acetylators, it is not yet clear that procainamide is metabolized by a bimodally distributed enzyme as is sulfamethazine.

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