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Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity.

ABSTRACT: Morbid obesity and bariatric surgery induce anatomical, physiological and metabolic alterations that may alter the body's disposition of drugs. Current literature on this topic is limited and sometimes inconsistent. Cytochrome P450 (CYP) is a superfamily of enzymes that metabolize around 75% of all marketed drugs. The purpose of this study was to evaluate the impact of body mass index and bariatric surgery on CYP activities. Firstly, we evaluated the in vivo activity of 4 major CYP isoenzymes (CYP2D6, CYP3A4, CYP2C9, and CYP1A2) in normal weight, overweight, and morbidly obese individuals. Secondly, we assessed the short- (1 month) and medium-term (6 month) effects of the most commonly employed bariatric surgery techniques (laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) on the activity of these enzymes. CYP3A4 activity was lower in morbidly obese individuals, compared to normal-weight controls. Interestingly, bariatric surgery normalized CYP3A4 activity. In comparison with normal-weight controls, morbidly obese individuals had higher CYP2D6 activity, which was only observed in individuals with two functional alleles for this isoenzyme. Neither body mass index nor surgery had significant effects on CYP2C9 and CYP1A2 activities. Overall, no relevant differences in CYP activities were found between surgical techniques. In conclusion, further studies should evaluate whether the observed alterations in CYP3A4 activity will require dose adjustments for CYP3A4 substrates especially in morbidly obese individuals before and after bariatric surgery.

SUBMITTER: Rodriguez-Morato J

PROVIDER: S-EPMC6938522 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity.

Rodríguez-Morató Jose J Goday Albert A Langohr Klaus K Pujadas Mitona M Civit Ester E Pérez-Mañá Clara C Papaseit Esther E Ramon Jose Manuel JM Benaiges David D Castañer Olga O Farré Magí M de la Torre Rafael R

Scientific reports 20191231 1

Morbid obesity and bariatric surgery induce anatomical, physiological and metabolic alterations that may alter the body's disposition of drugs. Current literature on this topic is limited and sometimes inconsistent. Cytochrome P450 (CYP) is a superfamily of enzymes that metabolize around 75% of all marketed drugs. The purpose of this study was to evaluate the impact of body mass index and bariatric surgery on CYP activities. Firstly, we evaluated the in vivo activity of 4 major CYP isoenzymes (C ...[more]

PMID: 31892725

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Project description:BACKGROUND:Morbid obesity is associated with an increased risk of thrombotic events, which has been attributed to increased thrombotic activity. Multiple mechanisms have been proposed to explain this increased risk, including an inflammatory state with upregulation of procoagulant and antifibrinolytic proteins. We therefore hypothesize that patients with morbid obesity are hypercoagulable and will revert to normal after bariatric surgery. OBJECTIVES:To evaluate changes in the hypercoagulable state after bariatric surgery. SETTING:University Hospital, Bariatric Center of Excellence, United States. METHODS:Thromboelastography (TEG) data were collected on 72 subjects with morbid obesity, with 36 who had 6 months of follow-up after bariatric surgery. TEG data of 75 healthy subjects (HS) without obesity, recent trauma or surgery, acute infection, or chronic conditions (e.g., liver, cardiovascular, or kidney disease; cancer; diabetes; autoimmune or inflammatory disorders; and disorders of coagulation) were used for comparison. TEG was performed alone and with the addition of 75 and 150 ng/mL tissue plasminogen activator (tPA) to quantify fibrinolysis resistance (tPA-challenged TEG). RESULTS:The bariatric surgery cohort had a median age of 40.5 years, a median body mass index of 44.6 kg/m2, and 90% female patients. Median body mass index reduced significantly 6 months post surgery but remained elevated compared with the HS group (31.4 versus 25.4 kg/m2, P < .0001). At 6 months post surgery, subjects had longer reaction time (mean difference, 1.3; P = .02), lower maximum amplitude (-2.4, P = .01), and increased fibrinolysis with low-dose (3.1, P < .0001) and high-dose tPA-challenged TEG (9, P < .0001). Compared with HS, the postsurgery TEG values were still more likely to be abnormal (all P < .05). CONCLUSIONS:Patients with morbid obesity form stronger clots more rapidly and are more resistant to fibrinolysis than subjects without obesity. Bariatric surgery significantly improved the hypercoagulable profile and fibrinolysis resistance of morbid obesity.

Dataset Information

Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity.

Publications

Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity.

Similar Datasets

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