Pharmacokinetics and acetylation of sulfa‐2‐monomethoxine in humans

In humans sulfa‐2‐monomethoxine (S) is metabolized by N 4 ‐acetylation (39.9 ± 8.0 per cent). After an oral dose, S is eliminated biphasically (t ½ , 5·2 ± 1·6h and 13·2 ± 3·4h) which is similar in both fast and slow acetylators. The metabolite N 4 ‐acetylsulfa‐2‐monomethoxine (N 4 ) is eliminated monophasically (t ½ , 30·0 ± 5·7h). The intrinsic mean residence time (MRT) of NM 4 is 33·5 ±8·8h. The mean total body clearance of S is 11·6 ±2·7 ml min −1 , and the Vd ss is 12·3 ± 1·01. The renal clearance of S during the first day was twice as high as on the following days for two of the six volunteers (8 vs 4 ml min −1 ). The renal clearance of N 4 during the first day, for four out of the six volunteers, was twice as high as on the following days (8 vs 4 ml min −1 ). The protein binding of S is 95 per cent and that of its conjugate N 4 98 per cent. Approximately 80 per cent of the oral dose of S is excreted in the urine as parent drug (41·0 ± 6·2 per cent) and as N 4 acetyl conjugate (39·9 ± 8·0 per cent).