Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach

Abstract

The inter-individual variability of CYP450s enzyme activity may be reduced by comparing the effects of bariatric surgery on CYP-mediated drug elimination in comparable patients before and after surgery. The current research will use a low-dose phenotyping cocktail to simultaneously evaluate the activities of six CYP isoforms and P-gp. The results showed that following weight reduction after surgery, the activity of all enzymes increased compared to the obese period, which was statistically significant in the case of CYP3A, CYP2B6, CYP2C9, and CYP1A2. Furthermore, the activity of P-gp after surgery decreased without reaching a statistical significance (p-value > 0.05). Obese individuals had decreased CYP3A and CYP2D6 activity compared with the control group, although only CYP3A was statistically important. In addition, there was a trend toward increased activity for CYP1A2, CYP2B6, CYP2C9, and CYP2C19 in obese patients compared to the control group, without reaching statistical insignificance (p-value ≥ 0.05). After six months (at least), all enzymes and the P-gp pump activity were significantly higher than the control group except for CYP2D6. Ultimately, a greater comprehension of phenoconversion can aid in altering the patient’s treatment. Further studies are required to confirm the changes in the metabolic ratios of probes after bariatric surgery to demonstrate the findings’ clinical application. As a result, the effects of inflammation-induced phenoconversion on medication metabolism may differ greatly across persons and drug CYP pathways. It is essential to apply these results to the clinic to recommend dose adjustments.