Evaluation of phenoconversion phenomenon in obese patients: the effects of bariatric surgery on the CYP450 activity “a protocol for a case–control pharmacokinetic study”

Personalized therapy suggests the appropriate drug at the right dose for the first time through genotype-based individualized therapy, instead of prescribing medicines by the traditional one-size-fits-all manner, thereby claiming that it will make medicines safer and more effective. Accordingly, polymorphisms of drug metabolizing enzymes (DMEs), which induce inter-individual variability in the pharmacokinetics of a drug, have attracted great interest in the context of personalized medicine. Obesity is one of the most common chronic diseases in the world, including Iran, and the prevalence is increasing according to predictions. The remarkable role of P450 cytochromes has been verified in the metabolism of numerous drugs, toxins, carcinogen compounds, and the synthesis of some intrinsic compounds, such as steroid hormones. Thus, evaluating the activity of these enzymes is of great importance because any functionality variation can lead to failure in the treatment or unwanted side effects of some drugs. Therefore, any change in the activity of these enzymes in obese patients can also be problematic in the treatment process of these patients in comparison to normal weighted ones. Since only a few human studies have examined the role of inflammation in altering the function of these enzymes, it seems to be necessary to investigate the effect of obesity on the expression and activity of these enzymes; in which the role of inflammatory processes has been proven. Most importantly, it is worth evaluating changes in the activity levels of cytochrome P450 (CYP450) and the inflammatory cytokines after a course of post-surgical treatment and weight loss. To evaluate the activity of CYPs, a multi-drug cocktail is prescribed to obese patients before and after obesity surgery, as well as to healthy volunteers, to provide simultaneous evaluation of different isoforms. A complete demographic data, medical examinations, laboratory tests, and the CYPs genotype of all participants can be extremely important during this investigation.