The effect of obesity on drug metabolism in African‐American children

Abstract

It is well established that oxidative enzyme activity differs between obese and healthy weight adults. However, the effect of obesity on drug metabolism in children is poorly understood. Therefore this study examined whether obese and healthy weight children vary with respect to phase I enzyme activity. In vivo CYP 1A2, 3A and 2D6 enzyme activity was assessed in African‐American children between the ages of 6–10yrs by measuring administered dextromethorphan (0.5mg/kg; max=30 mg) and caffeine (11.5mg). Cumulative 8hr metabolic urine ratios (MR) of dextromethorphan/dextrorphan and dextromethorphan/3‐methoxymorphinan were used to determine CYP 2D6 and 3A activity, respectively. Caffeine oral salivary clearance (Dose/AUC0–8) was used to determine CYP 1A2 activity. Nine healthy weight and 6 obese children were evaluated. The median (range) of CYP 3A MR was 2.08 (0.54–7.36) vs. 9.21 (1.24–19.92) in healthy weight and obese children, respectively. CYP 2D6 MR was 0.0378 (0.0018–0.2144) in healthy weight children and 0.1839 (0.0077–0.9657) in obese children. Obese children trended toward a higher oral clearance of caffeine with a median (range) of 0.0064 (0.0021–0.0192) L/hr vs. 0.0040 (0.0013–0.0066) L/hr. These preliminary results suggest that there may be a phenotypic difference in CYP 3A, 2D6, and 1A2 enzyme activity between healthy weight and obese children. Research supported by K12HD052187‐01.