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Scleroderma is associated with differences in individual routes of drug metabolism: A study with dapsone, debrisoquin, and mephenytoin
Author(s) -
May D Gail,
Black Carol M,
Olsen Nancy J,
Csuka Mary E,
Tanner S Bobo,
Bellino Lisa,
Porter James A,
Wilkinson Grant R,
Branch Robert A
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.151
Subject(s) - mephenytoin , dapsone , scleroderma (fungus) , pharmacology , drug , in vivo , medicine , immunology , metabolism , biology , cyp2c19 , cytochrome p450 , inoculation , microbiology and biotechnology
Exposure to certain environmental agents may induce a scleroderma‐like syndrome in a small proportion of individuals. Differences in susceptibility could involve metabolic activation of a protoxin, with affected patients having a greater converting ability. This possibility was investigated in 84 patients with scleroderma and 108 control subjects with in vivo probes of specific pathways of metabolism. Scleroderma was associated with reduced hydroxylating activity for dapsone and S‐mephenytoin, whereas the ability to hydroxylate debrisoquin and N‐acetyl dapsone was similar in both groups. Logistic regression confirmed these associations based on the shift in frequency distribution. Individuals who were poor metabolizers for mephenytoin and only modest N‐hydroxylators of dapsone had a tenfold increased risk of scleroderma (p = 0.008). Thus this combined metabolic impairment may be causally involved in the development of scleroderma or, alternatively, the disease may produce inhibition of selected metabolizing enzymes in a subset of patients. Clinical Pharmacology and Therapeutics (1990) 48, 286–295; doi: 10.1038/clpt.1990.151