Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome
- PMID: 306574
- DOI: 10.1056/NEJM197805252982101
Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome
Abstract
To investigate the relation between acetvlator phenotype and the development of procainamide-induced lupus, we determined the rate of development of antinuclear antibodies in 20 patients of known acetylator phenotype receiving chronic procainamide therapy. The duration of therapy required to induce antibodies in 50 per cent of slow (11) and rapid (nine) acetylators was 2.9 and 7.3 months respectively. The median total dose that produced ant;bodies was 1.5 g per kilogram and 6.1 g per kilogram respectively. After one year antibodies had developed in 18 patients. Retrospective studies of patients in whom procainamide lupus had developed revealed that the duration of therapy required for induction in 14 slow and seven rapid acetylators was 12 +/- 5 and 48 +/- 22 months respectively (P less than 0.002). We conclude that acetylator phenotype influences the rate at which procainamide induces antinuclear antibodies and probably the lupus syndrome. Antibody production is probably related to the parent compound or a non-acetylated metabolite.
Similar articles
-
Procainamide, N-acetylprocainamide, antinuclear antibody and systemic lupus erythematosus.Angiology. 1986 Dec;37(12 Pt 2):968-71. Angiology. 1986. PMID: 2433971
-
Antinuclear antibodies related to acetylator phenotype in mice.J Pharmacol Exp Ther. 1980 Jun;213(3):485-90. J Pharmacol Exp Ther. 1980. PMID: 6970809
-
Procainamide-induced lupus erythematosus-like syndrome in relation to acetylator phenotype and plasma levels of procainamide.Acta Med Scand. 1979;206(4):245-51. doi: 10.1111/j.0954-6820.1979.tb13505.x. Acta Med Scand. 1979. PMID: 92167
-
Drug-induced systemic lupus erythematosus.Prog Clin Immunol. 1980;4:1-21. Prog Clin Immunol. 1980. PMID: 6992215 Review.
-
Acetylator phenotype and lupus erythematosus.Clin Pharmacokinet. 1981 Mar-Apr;6(2):118-34. doi: 10.2165/00003088-198106020-00003. Clin Pharmacokinet. 1981. PMID: 7011656 Review.
Cited by
-
Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities.Nat Commun. 2016 Sep 22;7:12777. doi: 10.1038/ncomms12777. Nat Commun. 2016. PMID: 27652979 Free PMC article.
-
Metabolism of procainamide to the cytotoxic hydroxylamine by neutrophils activated in vitro.J Clin Invest. 1989 Apr;83(4):1336-43. doi: 10.1172/JCI114020. J Clin Invest. 1989. PMID: 2539397 Free PMC article.
-
Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review.Expert Opin Drug Metab Toxicol. 2021 Jan;17(1):9-21. doi: 10.1080/17425255.2021.1840551. Epub 2020 Nov 3. Expert Opin Drug Metab Toxicol. 2021. PMID: 33094670 Free PMC article. Review.
-
Idiosyncratic drug reactions: possible role of reactive metabolites generated by leukocytes.Pharm Res. 1989 Apr;6(4):265-73. doi: 10.1023/a:1015934104984. Pharm Res. 1989. PMID: 2664753 Review.
-
Drug-induced lupus erythematosus: an update on drugs and mechanisms.Curr Opin Rheumatol. 2018 Sep;30(5):490-497. doi: 10.1097/BOR.0000000000000522. Curr Opin Rheumatol. 2018. PMID: 29870500 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources