Abstract
It is well established that oxidative enzyme activity differs between obese and healthy weight adults. This study examined the interaction between age and obesity using a rat model of obesity on the developmental profiles of intrinsic clearance of hepatic phase 1 enzyme activity. Liver microsomes were isolated from OLETF(obese)/LETO(lean) at various weeks of age. CYP 1A2, CYP 2E1, CYP 2D2, and xanthine oxidase (XO) enzyme activity was assessed using probe substrates. Both age and obesity effects were tested for significance (p‐value ¡Ü0.05). Age related differences were observed in all enzymes characterized (p<0.004) within both the lean and obese groups. Obese rats had a 25% greater total exposure to 1A2 activity when compared to the lean (p=0.017). Conversely, obese rats had 30% less total exposure to 2D2 activity when compared to the lean (p=0.0002). There were no statistical differences in total exposure for 2E1 or XO between the lean and obese groups p=0.082 and 0.060, respectively. The results indicate that alterations in enzymatic drug metabolism are dependent on both age and obesity status. The changes observed are unique to CYP 1A2 and CYP 2D2 and may provide further insight towards the impact of age and obesity on drug metabolism in humans. Research was supported by University of Minnesota College of Pharmacy.
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