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Human liver xanthine oxidase: Nature and extent of individual variation
Author(s) -
Guerciolini Roberto,
Szumlanski Carol,
Weinshilboum Richard M
Publication year - 1991
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.1991.205
Subject(s) - xanthine oxidase , variation (astronomy) , chemistry , biochemistry , enzyme , physics , astrophysics
Xanthine oxidase catalyzes the biotransformation of many drugs, including the thiopurines and methylxanthines. We used a sensitive radiochemical assay to determine optimal conditions for the assay of human liver xanthine oxidase activity. We then used those assay conditions to study the nature and extent of individual variation of xanthine oxidase activity in 189 samples of hepatic tissue from patients undergoing clinically indicated partial hepatectomy or open liver biopsy. The average hepatic xanthine oxidase activity was 21% higher in samples from male patients than in those from female patients (1.27 ± 0.43 [mean ± SD, n = 92] versus 1.05 ± 0.38 U/gm tissue [ n = 97, p < 0.0001], respectively). Seventynine of these tissue samples had been obtained from patients with normal liver function studies and normal serum creatinine values. Average xanthine oxidase activity in these 79 samples remained approximately 20% higher for men than for women (1.35 ± 0.38 versus 1.12 ± 0.33 U/gm tissue, respectively). Probit analysis of the data for samples from patients with normal liver function studies and normal creatinine values suggested the presence of a subgroup of samples with relatively low xanthine oxidase activity in 21% (9 of 42) of male patients and 27% (10 of 37) of female patients. These observations may have implications with regard to individual variation in the biotransformation of drugs metabolized by xanthine oxidase. Clinical Pharmacology and Therapeutics (1991) 50 , 663–672; doi: 10.1038/clpt.1991.205