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Microsomal hydroxylation as measured by pentobarbital elimination in patients with idiopathic systemic lupus erythematosus
Author(s) -
Drayer Dennis E,
Lorenzo Beverly,
Lahita Robert G,
Robbins William C,
Reidenberg Marcus M
Publication year - 1982
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.1982.147
Subject(s) - pentobarbital , systemic lupus erythematosus , microsome , chemistry , lupus erythematosus , medicine , endocrinology , metabolism , drug , volume of distribution , hydroxylation , pharmacology , biochemistry , pharmacokinetics , immunology , enzyme , antibody , disease
A mechanism postulated for drug‐ or chemical‐induced systemic lupus erythematosus (SLE) is that the chemical is covalently bound to nuclear macromolecules increasing the immunogenicity of the macromolecule. This may require metabolic activation by oxidation. There are many similarities between drug‐induced and idiopathic SLE. Twelve patients with idiopathic SLE and 12 normal subjects were given 100 mg pentobarbital orally to evaluate their microsomal hydroxylating activity. Plasma pentobarbital concentration was measured by gas‐liquid chromatography. Mean plasma pentobarbital half‐life was 24 ± 10 (mean ± SD) hr in the SLE patients, which is only slightly shorter than the 26 ± 12 hr in the control subjects. The mean apparent volume of distribution in the patients was 1.28 ± 0.30 l/kg, which is slightly above the 1.00 ± 0.37 l/kg in the normal subjects (P < 0.05). Mean metabolic clearance rate in the SLE patients was 0.045 ± 0.022 l/hr/kg, which is more than the 0.028 ± 0.008 l/hr/kg in the normal control subjects (P < 0.02). Since the metabolic clearance rate of a drug is the proper value for evaluating metabolism rate, we conclude that patients with SLE have an increased elimination rate for drugs or other foreign compounds that are biotransformed by microsomal oxidation and may more rapidly bioactivate chemicals to reactive compounds. Clinical Pharmacology and Therapeutics (1982) 32, 195–200; doi: 10.1038/clpt.1982.147