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Racial and gender differences in N ‐acetyltransferase, xanthine oxidase, and CYP1A2 * activities
Author(s) -
Relling Mary V,
Lin Jinsying,
Ayers Gregory D,
Evans William E
Publication year - 1992
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.1992.203
Subject(s) - xanthine oxidase , cyp1a2 , chemistry , caffeine , endocrinology , medicine , urine , paraxanthine , enzyme , biochemistry , biology , cytochrome p450
Background The urinary molar concentration ratios of several caffeine metabolites are indicators of specific drug metabolizing enzyme activities. The ratios of 5‐acetyl‐amino‐6‐formylamino‐3‐methyluracil (AFMU) to 1‐methylxanthine (1X), AFMU to 1X plus 1‐methyluric acid (1U), and AFMU to 1X + 1U + AFMU are indicative of N ‐acetyltransferase (NAT) activity; the ratios of 1U to 1X and 1U to 1U + 1X indicate xanthine oxidase activity; and the ratio of the sum of 7‐demethylated metabolites (AFMU + 1X + 1U) to the precursor for all three compounds, paraxanthine (PX), is a putative indicator of CYP1A2 oxidative activity. Our objective was to discern whether there are race‐, gender‐, and age‐related differences in these indexes of drug‐metabolizing activity. Methods In 342 normal healthy unrelated subjects, metabolites were measured in urine collected after administration of low‐dose caffeine. Results By two‐way analysis of variance, NAT activity was higher in black subjects than in white subjects when assessed as AFMU/(1U + 1X) or as AFMU/(AFMU + 1U + 1X) (p = 0.001 and p = 0.002, respectively), but less so by use of AFMU/1X (p = 0.08). Xanthine oxidase activity, as assessed by 1U/1X or as 1U/(1U + IX), was lower in black subjects than in white subjects (p = 0.02 and/> = 0.001, respectively) and was lower in males than in females (p = 0.001 for both ratios). Females had higher AFMU/1X ratios (p = 0.03) because of higher xanthine oxidase activity. In a model in which AFMU/1X was the dependent variable and race, sex, age, and an index of xanthine oxidase (1U/1X) were independent variables, only race and 1U/1X were significant determinants of this NAT index (p = 0.003 and p < 0.001, respectively). The CYP1A2 ratio was lower in black subjects (p = 0.036) and in females (p = 0.015). Conclusion Racial and gender differences in xanthine oxidase activity render the AFMU/1X ratio less reliable as an assessment of NAT activity in a heterogeneous population compared with the AFMU/(1U + 1X) or AFMU/(AFMU + 1U + 1X) ratios. The observed racial and gender differences in NAT, xanthine oxidase, and CYP1A2 activities may have implications for racial and gender differences in drug effects and carcinogen biotransformation. Clinical Pharmacology and Therapeutics (1992) 52 , 643–658; doi: 10.1038/clpt.1992.203