Altered xanthine oxidase and N‐acetyltransferase activity in obese children

• DOI: 10.1111/j.1365-2125.2011.03959.x
• Publication Date: 2011-03-08T09:16:25Z
• Authors: Manoj S. Chiney; Sarah J. Schwarze...; L'Aurelle A. Johnson
• Keywords: 2. Zero hunger; Male; Xanthine Oxidase; Models, Statistical; Arylamine N-Acetyltransferase; Body Weight; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cytochrome P-450 CYP1A2; Caffeine; Case-Control Studies; Humans; Female; Obesity; Child; Biomarkers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• It has been well established that obese adults exhibit differences in expression and regulation of drug metabolizing enzymes as compared with healthy‐weight adults. However, as obesity is becoming a more prevalent problem in children, little, if any, information is available that specifically addresses the consequences of obesity on drug metabolism in this population.WHAT THIS STUDY ADDS• This is the first study that provides evidence for elevated levels of xanthine oxidase and N‐acetyltransferase 2 enzyme activity in children who are obese. This new knowledge may provide insight into improving dosing strategies in obese children with concomitant diseases who are treated with therapeutic agents that are metabolized by these enzymes.AIMSIt 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).METHODSIn vivoCYP1A2, 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.RESULTSSixteen 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 ± 0.06vs.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).CONCLUSIONSThis 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.