Pharmacokinetics, acetylation‐deacetylation, renal clearance, and protein binding of sulphamerazine, N 4 ‐acetylsulphamerazine, and N 4 ‐trideuteroacetylsulphamerazine in ‘fast’ and ‘slow’ acetylators

Sulphamerazine shows a clear acetylator phenotype. The half‐life of elimination of sulphamerazine is 12 h in ‘fast’ and 24 h in ‘slow’ acetylators. N 4 ‐Acetylsulphamerazine is eliminated biphasically, characterized by half‐lives of 5 and 12 h in ‘fast’ and 5 and 24 h in ‘slow’ acetylators. Protein binding of sulphamerazine (86 per cent) and N 4 ‐acetylsulphamerazine (92 per cent) is independent of acetylator phenotype or the origin of the compound, whether it is present in the body as parent compound or metabolite. The renal clearance of sulphamerazine (20ml min −1 ) and N 4 ‐acetylsulphamerazine (300–500 ml min −1 ) is independent of the acetylator type and the origin of the compound. The existence of an acetylation‐deacetylation equilibrium in the metabolism of sulphamerazine has been demonstrated with the test drug N 4 ‐trideuteroacetylsulpha‐ merazine, which inhibits the renal excretion and clearance of N 4 ‐acetylsulphamerazine.