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Effect of Acetylator Phenotype on the Rate at Which Procainamide Induces Antinuclear Antibodies and the Lupus Syndrome

List of authors.
  • Raymond L. Woosley, M.D., Ph.D.,
  • Dennis E. Drayer, Ph.D.,
  • Marcus M. Reidenberg, M.D.,
  • Alan S. Nies, M.D.,
  • K. Carr, M.S.,
  • and John A. Oates, M.D.

Abstract

To investigate the relation between acetylator 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 antibodies 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<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. (N Engl J Med 298:1157–1159, 1978)

Funding and Disclosures

Supported in part by grants from the Tennessee Heart Association, grants (GM 15431, GM 00113, 5 M01-RR 95, GM 22193 and 5 S01 RR 05396) from the U.S. Public Health Service and a quinidine research grant from the U.S. District Court of Eastern Pennsylvania and its settlement fund from antitrust litigation against quinidine producers.

Dr. Nies is a Burroughs Wellcome Scholar in Clinical Pharmacology.

We are indebted to Ms. Lonnie Grassman, MT (ASCP), and Kathleen Restivo, M.S., for technical assistance.

Author Affiliations

From the departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN, and the departments of Medicine and Pharmacology, Cornell University Medical College, New York, NY (address reprint requests to Dr. Woosley at the Division of Clinical Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232).

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