N-Acetyltransferases: Pharmacogenetics and clinical consequences of polymorphic drug metabolism

Journal of Pharmacokinetics and Biopharmaceutics

Volumn 24, Issue 5, 1996, Pages 509-519

  Spielberg, Stephen P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Hydroxylamine metabolites; N acetyltransferase; NAT1; NAT2; Sulfonamide hypersensitivity reactions

Indexed keywords

ACYLTRANSFERASE; CYTOCHROME P450; SULFAMETHOXAZOLE; SULFONAMIDE;

CARCINOGENESIS; CYTOTOXICITY; DRUG DEVELOPMENT; DRUG METABOLISM; ENZYME ACTIVITY; GENETIC POLYMORPHISM; HUMAN; IMMUNE RESPONSE; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

ALLELES; ANIMALS; ANTI-INFECTIVE AGENTS; ARYLAMINE N-ACETYLTRANSFERASE; CHROMOSOMES, HUMAN, PAIR 8; CYTOCHROME P-450 ENZYME SYSTEM; DOGS; DRUG DESIGN; GENOTYPE; HUMANS; IODIDE PEROXIDASE; MUTAGENICITY TESTS; PEROXIDASE; PHARMACOGENETICS; PHENOTYPE; POLYMORPHISM, GENETIC; SULFONAMIDES; VARIATION (GENETICS);

EID: 0030426571     PISSN: 0090466X     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF02353477     Document Type: Review

References (40)

1. W. W. Weber. The Acetylator Genes and Drug Response, Oxford University Press, New York, 1987.
2. D. A. P. Evans. N-acetyltransferases. Pharmacol. Ther. 42:157-234 (1989).
3. K. P. Vatsis, W. W. Weber, D. A. Bell et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 5:1-17 (1995).
4. H. B. Hughes. Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Am. Rev. Tuberculosis 70:266-273 (1954).
5. D. A. P. Evans, K. A. Manley, and V. A. McKusick. Genetic control of isoniazid metabolism in man. Br. Med. J. 2:485-491 (1960).
6. M. Blum, D. M. Grant, O. W. McBride, M. Heim, and U. A. Meyer. Human arylamine N-acetyltransferase genes: Isolation, chromosomal localization and functional expression. DNA Cell Biol. 9:193-203 (1990).
7. T. Deguchi, M. Mashimo, and T. Suzuki. Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver. J. Biol. Chem. 265:12757-12760 (1990).
8. S. Ohsako and T. Deguchi. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. J. Biol. Chem. 265:4630-4634 (1990).
9. M. Blum, A. Demierre, D. M. Grant, H. Heim, and U. A. Meyer. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc. Natl. Acad. Sci. U.S. 88:5237-5241 (1991).
10. D. Hickman and E. Sim. N-acetyltransferase polymorphism: Comparison of phenotype and genotype in humans. Biochem. Pharmacol. 42:1007-1014 (1991).
11. K. P. Vatsis, K. J. Martell, and W. W. Weber. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc. Natl. Acad. Sci. U.S. 88:6333-6337 (1991).
12. D. M. Grant, B. K. Tang, and W. Kalow. A simple test for acetylator phenotype using caffeine. Br. J. Clin. Pharmacol. 17:459-464 (1984).
13. D. Hein, R. Ferguson, M. Doll et al. Molecular genetics of human polymorphic N-acetyltransferase: Enzymatic analysis of 15 recombinant wild-type, mutant, and chimeric NAT2 allozymes. Hum. Mol. Genet. 3:729-734 (1994).
14. D. M. Grant, K. Morike, M. Eichelbaum, and U. A. Meyer. Acetylation pharmacogenetics: The slow acetylator phenotype is caused by decreased or absent arylamine N-acetyltransferase in human liver. J. Clin. Invest. 85:968-972 (1990).
15. D. M. Grant, M. Blum, M. Beer, and U. A. Meyer. Monomorphic and polymorphic human arylamine N-acetyltransferases: A comparison of liver isozymes and expressed products of two cloned genes. Mol. Pharmacol. 39:184-191 (1991).
16. D. M. Grant, P. Vohra, Y. Avis, and A. Ima. Detection of a new polymorphism of human N-acetyltransferase NAT1 using p-aminosalicyclic acid as an in vivo probe. J. Basic Clin. Physiol. Pharmacol. 3:244 (1992).
17. K. P. Vatsis and W. W. Weber. Structural heterogeneity of caucasian N-acetyltransferase at the NAT1 gene locus. Arch. Biochem. Biophys. 310:71-76 (1993).
18. N. Hughes and D. M. Grant. Cloning and expression of new mutant forms of human N-acetyltransferase NAT1 with defective function. 10th International Symposium on Microsomes and Drug Oxidations, Toronto, 1994, p. 278.
19. B. L. Lee, D. Wong, N. L. Benowitz, and P. M. Sullam. Altered patterns of drug metabolism in patients with the acquired immunodeficiency syndrome. Clin. Pharmacol. Ther. 53:529-535 (1993).
20. D. M. Grant, P. D. Josephy, H. L. Lord, and L. D. Morrison. Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: Metabolic and mutagenic activation of aromatic amines. Cancer Res. 52:3961-3964 (1992).
21. D. E. Drayer and M. M. Reidenberg. Clinical consequences of polymorphic acetylation of drugs. Clin. Pharmacol. Ther. 22:251-258 (1977).
22. N. H. Shear, S. P. Spielberg, D. M. Grant, B. K. Tang, and W. Kalow. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann. Intern. Med. 105:179-184 (1986).
23. M. J. Rieder, N. H. Shear, A. Kanee, B. K. Tang, W. Kalow, and S. P. Spielberg. Predominance of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions. Clin. Pharmacol. Ther. 49:13-17 (1991).
24. N. H. Shear and S. P. Spielberg. In vitro evaluation of a toxic metabolite of sulfadiazine. Can. J. Physiol. Pharmacol. 63:1370-1372 (1985).
25. A. E. Cribb and S. P. Spielberg. Hepatic microsomal metabolism of sulfamethoxazole to the hydroxylamine. Drug. Metab. Disp. 18:784-787 (1990).
26. A. E. Cribb, M. Miller, A. Tesoro, and S. P. Spielberg. Peroxidase-dependent oxidation of sulfonamides by monocytes and neutrophils from man and dog. Mol. Pharmacol. 38:744-751 (1990).
27. A. Gupta, M. M. Eggo, J. P. Uetrecht et al. Drug-induced hypothyroidism: The thyroid as a target organ in hypersensitivity reactions to anticonvulsants and sulfonamides. Clin. Pharmacol. Ther. 51:56-67 (1992).
28. A. E. Cribb and S. P. Spielberg. Sulfamethoxazole is metabolized to the hydroxylamine in humans. Clin. Pharmacol. Ther. 51:522-526 (1992).
29. A. E. Cribb, S. P. Spielberg, and G. P. Griffin. N4-Hydroxylation of sulfamethoxazole by cytochrome P450 of the CYP2C subfamily, and reduction of sulfamethoxazole in human and rat hepatic microsomes. Drug Metab. Disp. 23:406-414 (1995).
30. M. J. Rieder, J. P. Uetrecht, and S. P. Spielberg. Synthesis and toxicity of hydroxylamines of the sulfonamides. J. Pharmacol. Exp. Ther. 244:724-728 (1988).
31. M. J. Rieder, J. P. Uetrecht, N. H. Shear, M. Cannon, M. Miller, and S. P. Spielberg. Diagnosis of sulfonamide hypersensitivity reactions by in vitro "re-challenge" with hydroxylamine metabolites. Ann. Intern. Med. 110:286-289 (1989).
32. U. Giger, L. L. Werner, N. J. Millichamp, and N. T. Gorman. Sulfadiazine-induced allergy in six Doberman Pinschers. J. Am. Vet. Med. Assoc. 186:479-484 (1985).
33. A. E. Cribb and S. P. Spielberg. An in vitro investigation of predisposition to sulfonamide idiosyncratic toxicity in dogs. Vet. Res. Commun. 14:241-252 (1990).
34. A. E. Cribb, M. A. Miller, J. S. Leeder, and S. P. Spielberg. Reactions of the nitroso and hydroxylamine metabolites of sulfamethoxazole with reduced glutathione: Implications for idiosyncratic toxicity. Drug Metab. Disp. 19:900-906 (1991).
35. R. Riley, A. E. Cribb, and S. P. Spielberg. Glutathione-S-transferase mu is not a marker for sulfonamide hypersensitivity reactions. Biochem. Pharmacol. 42:696-698 (1991).
36. R. Buhl, H. A. Jaffe, K. J. Holroyd et al. Systemic glutathione deficiency in symptomfree HIV seropositive individuals. Lancet 2:1294-1298 (1989).
37. F. M. Gordon, G. L. Simon, C. B. Wofsy, and J. Mills. Adverse reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann. Intern. Med. 100:495-499 (1984).
38. I. Medina, J. Mills, G. Leoung et al. Oral therapy for pneunocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole vs. trimethoprim-dapsone. New Engl. J. Med. 323:776-782 (1990).
39. H. Nakamura, J. Uetrecht, D. M. Grant, and S. P. Spielberg. Metabolism and toxicity of N-acetoxy-sulfamethoxazole. J. Pharmacol. Exp. Ther. 274:1099-1104 (1995).
40. A. E. Cribb, D. M. Grant, and S. P. Spielberg. Expression of the monomorphic arylamine N-acetyltransferase (NAT1) in human leukocytes. J. Pharmacol. Exp. Ther. 259:1241-1246 (1991).