Microsomal hydroxylation as measured by pentobarbital elimination in patients with idiopathic systemic lupus...

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 subject (P less than 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 less than 0.02). Since the metabolic clearance rate of a drug is the proper value for evaluating metabolism rate, we conclude that patients with SLE hve 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.