Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity
| Autor: | Magí Farré, Olga Castañer, Clara Pérez-Mañá, Jose Rodríguez-Morató, Mitona Pujadas, Esther Papaseit, David Benaiges, Rafael de la Torre, Ester Civit, Albert Goday, Klaus Langohr, José M. Ramón |
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| Přispěvatelé: | Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. GRBIO - Grup de Recerca en Bioestadística i Bioinformàtica |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty CYP2D6 Biomatemàtica lcsh:Medicine Matemàtiques i estadística::Matemàtica aplicada a les ciències [Àrees temàtiques de la UPC] Bariatric Surgery Overweight 030226 pharmacology & pharmacy Article Phase II trials Medium term Morbid obesity Young Adult 03 medical and health sciences 0302 clinical medicine Cytochrome P-450 CYP1A2 medicine Cytochrome P-450 CYP3A Humans Obesity lcsh:Science CYP2C9 Cytochrome P-450 CYP2C9 Biomathematics 2. Zero hunger Multidisciplinary CYP3A4 business.industry lcsh:R 92 Biology and other natural sciences::92B Mathematical biology in general [Classificació AMS] CYP1A2 Middle Aged Obesity Morbid 3. Good health Surgery Treatment Outcome Cytochrome P-450 CYP2D6 030220 oncology & carcinogenesis lcsh:Q Female medicine.symptom business Body mass index |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Scientific Reports Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) UPCommons. Portal del coneixement obert de la UPC Universitat Politècnica de Catalunya (UPC) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
| Popis: | 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. This work was supported by a grant from the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, FISS ETS PI08/90638 co-financed with European Union ERDF funds (European Regional Development Fund). It was also partially supported by grants MTM2015-64465-C2-1-R from the Ministerio de Economía y Competividad (Spain) and 2014 SGR 464 from the Departament d’Economia i Coneixement de la Generalitat de Catalunya (Spain). JRM acknowledges the EU Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant No. 712949 (TECNIOspring PLUS) from the Agency for Business Competitiveness of the Government of Catalonia. OCN and EPF had grants from ISCIII Juan Rodés JR17/00022 and JR 16/00020. |
| Databáze: | OpenAIRE |
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