Kinetic phenotypic diagnosis of N-acetylation polymorphism in patients based on ratio of urinary metabolites of salicylazosulfapyridine

Koichi Yokogawa, Tohru Nakaharu, Junko Ishizaki, Eijiro Ozaki, Yasuo Takeda, Hiroshi Mabuchi, Ryo Matsushita, Kazuko Kimura, Emi Nakashima, Fujio Ichimura, Ken Ichi Miyamoto

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8 Citations (Scopus)


We found that N-acetylation polymorphism can be evaluated from the disposition kinetics of sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) and their acetylated metabolites generated by N-acetyltransferase (NAT2) after oral administration of salicylazosulfapyridine (SASP). In 126 Japanese subjects, the homozygote of NAT2*4 was the most frequent (40%), followed by heterozygotes of NAT2*4 and mutant genes (28% NAT2*4/*6A, 15% NAT2*4/*7B, and 2% NAT2*4/*5B). Combinations of mutant genes accounted for 16%. When the relationship between the molar ratio of N-acetyl-SP (Ac-SP)/SP or N-acetyl-5-ASA(Ac-5-ASA)/5-ASA in serum and five genotypes of polymorphic NAT2* was examined in patients who received multiple doses of SASP, the molar ratios of Ac-SP/SP, rather than Ac-5-ASA/5-ASA tended to decrease according to the classification of genotype. We calculated the pharmacokinetic parameters in healthy subjects with various genotypes of polymorphic NAT2* after a single p.o. administration of SASP, according to a model of the SP metabolic pathways. The molar ratios of Ac-SP/SP in serum and urine were simulated using these parameters, and the molar ratio of Ac-SP/SP in urine at 4 days after the first administration could be categorized into ranges that were specific to various NAT2* genotypes. Thus, we were able to predict the N-acetylation polymorphic genotypes of patients by measuring the molar ratio of Ac-SP/SP in urine, after administration of SASP.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 2001 Oct 28


  • Genotype
  • NAT2*
  • Pharmacokinetics
  • Phenotype
  • Salicylazosulfapyridine

ASJC Scopus subject areas

  • Pharmaceutical Science


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