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Pharmacokinetics and acetylation of sulfa‐2‐monomethoxine in humans
Author(s) -
Vree Tom B.,
Kolmer Eleonora W. J. Beneken,
Hekster Yechiel A.,
Shimoda Minoru,
Ono Makoto,
Miura Tadayoshi
Publication year - 1992
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510130105
Subject(s) - pharmacokinetics , metabolite , urine , acetylation , medicine , chemistry , pharmacology , biochemistry , gene
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).