Altered xanthine oxidase and N-acetyltransferase activity in obese children

Br J Clin Pharmacol. 2011 Jul;72(1):109-15. doi: 10.1111/j.1365-2125.2011.03959.x.


Aims: It is well established that oxidative and conjugative enzyme activity differs between obese and healthy-weight adults. However, the effect of obesity on drug metabolism in children has not been studied extensively. This study examined whether obese and healthy-weight children vary with respect to oxidative enzyme activity of CYP1A2, xanthine oxidase (XO) and conjugative enzyme activity of N-acetyltransferase 2 (NAT2).

Methods: In vivo CYP1A2, XO and NAT2 activity was assessed in obese (n= 9) and lean (n= 16) children between the ages of 6-10 years using caffeine (118.3 ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8 h. Caffeine and metabolites were measured using LC/MS, and urinary metabolic ratios were determined based on reported methods.

Results: Sixteen healthy-weight and nine obese children were evaluated. XO activity was elevated in paediatric obese volunteers compared with non-obese paediatric volunteers (XO metabolic ratio of 0.7 ± 0.06 vs. 0.6 ± 0.06, respectively, 95% CI 0.046, 0.154, P < 0.001). NAT2 activity was fivefold higher in the obese (1 ± 0.4) as compared with non-obese children (0.2 ± 0.1), 95% CI 0.26, 1.34, P < 0.05. However, no difference was observed in CYP1A2 activity between the groups (95% CI -2.72, 0.12, P > 0.05).

Conclusions: This study provides evidence that obese children have elevated XO and NAT2 enzyme activity when compared with healthy-weight controls. Further studies are needed to determine how this may impact the efficacy of therapeutic agents that may undergo metabolism by these enzymes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arylamine N-Acetyltransferase / metabolism*
  • Biomarkers
  • Body Weight
  • Caffeine / urine
  • Case-Control Studies
  • Child
  • Cytochrome P-450 CYP1A2 / metabolism
  • Female
  • Humans
  • Male
  • Models, Statistical
  • Obesity / enzymology*
  • Xanthine Oxidase / metabolism*


  • Biomarkers
  • Caffeine
  • Cytochrome P-450 CYP1A2
  • Xanthine Oxidase
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human