Scleroderma is associated with differences in individual routes of drug metabolism: a study with dapsone, debrisoquin, and mephenytoin. Clin Pharmacol Ther 1990 Sep;48(3):286-95
Date
09/01/1990Pubmed ID
2401127DOI
10.1038/clpt.1990.151Scopus ID
2-s2.0-0025162357 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
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.
Author List
May DG, Black CM, Olsen NJ, Csuka ME, Tanner SB, Bellino L, Porter JA, Wilkinson GR, Branch RAAuthor
Mary Ellen Csuka MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylationAdult
Biotransformation
Dapsone
Debrisoquin
Disease Susceptibility
Female
Humans
Hydantoins
Hydroxylation
Isoquinolines
Logistic Models
London
Male
Mephenytoin
Middle Aged
Oxidation-Reduction
Scleroderma, Systemic
Tennessee
