TY - JOUR
T1 - Altered xanthine oxidase and N-acetyltransferase activity in obese children
AU - Chiney, Manoj S.
AU - Schwarzenberg, Sarah J.
AU - Johnson, L'Aurelle A.
PY - 2011/7
Y1 - 2011/7
N2 - 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 (118.3ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8h. 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.
AB - 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 (118.3ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8h. 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.
KW - Caffeine
KW - Drug metabolism
KW - Obesity
KW - Paediatric
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U2 - 10.1111/j.1365-2125.2011.03959.x
DO - 10.1111/j.1365-2125.2011.03959.x
M3 - Article
C2 - 21382071
AN - SCOPUS:79958752412
SN - 0306-5251
VL - 72
SP - 109
EP - 115
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 1
ER -