Human liver xanthine oxidase: nature and extent of individual variation.
Xanthine oxidase catalyzes the biotransformation of many drugs, including the thiopurines and methyl-xanthines. 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 less than 0.0001], respectively). Seventy-nine 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.
Guerciolini
R
R
Department of Pharmacology, Mayo Clinic/Foundation, Rochester, MN 55905.
Szumlanski
C
C
Weinshilboum
R M
RM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001711:Biotransformation; D002648:Child; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013048:Specimen Handling; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism*
D014527:Uric Acid; D014969:Xanthine Oxidase