Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity.
Por:
Rodríguez-Morató J, Goday A, Langohr K, Pujadas M, Civit E, Pérez-Mañá C, Papaseit E, Ramon JM, Benaiges D, Castañer O, Farré M and de la Torre R
Publicada:
31 dic 2019
Ahead of Print:
31 dic 2019
Categoría:
Multidisciplinary
Resumen:
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.
Filiaciones:
Rodríguez-Morató J:
Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, Barcelona, 08003, Spain
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, 28029, Madrid, Spain
Goday A:
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, 28029, Madrid, Spain
Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
Department of Medicine, Autonomous University of Barcelona, Cerdanyola, Spain
Cardiovascular Risk and Nutrition Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Langohr K:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Department of Statistics and Operations Research, Polytechnic University of Catalonia, Barcelona, Spain
Pujadas M:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, 28029, Madrid, Spain
Civit E:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Pérez-Mañá C:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Department of Pharmacology, Therapeutics and Toxicology, Autonomous University of Barcelona, Cerdanyola, Spain
Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol (HUGTP-IGTP), Badalona, Spain
:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Department of Pharmacology, Therapeutics and Toxicology, Autonomous University of Barcelona, Cerdanyola, Spain
Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol (HUGTP-IGTP), Badalona, Spain
Ramon JM:
Section of Gastrointestinal Surgery, Hospital del Mar, Barcelona, Spain
Benaiges D:
Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
Department of Medicine, Autonomous University of Barcelona, Cerdanyola, Spain
Cardiovascular Risk and Nutrition Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Castañer O:
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, 28029, Madrid, Spain
Cardiovascular Risk and Nutrition Research Group, IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
:
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain
Department of Pharmacology, Therapeutics and Toxicology, Autonomous University of Barcelona, Cerdanyola, Spain
Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol (HUGTP-IGTP), Badalona, Spain
de la Torre R:
Department of Experimental and Health Sciences, Universitat Pompeu Fabra (CEXS-UPF), Dr. Aiguader 80, Barcelona, 08003, Spain.
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program. IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona, 08003, Spain.
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto Salud Carlos III, 28029, Madrid, Spain.
Green Published, gold
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