Pharmacokinetics, acetylation-deacetylation, renal clearance, and protein binding of sulphamerazine, N4-acetylsulphamerazine, and N4-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. N4-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 N4-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 (20 ml min-1) and N4-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 N4-trideuteroacetylsulphamerazine, which inhibits the renal excretion and clearance of N4-acetylsulphamerazine.
D000107:Acetylation; D003404:Creatinine / Q000378:metabolism; D003640:Dealkylation; D003903:Deuterium; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010641:Phenotype; D011485:Protein Binding; D013416:Sulfamerazine / Q000031:analogs & derivatives* / Q000378:metabolism*
C037923:N(4)-acetylsulfamerazine; D003903:Deuterium; D003404:Creatinine; D013416:Sulfamerazine