نبذة مختصرة : 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 ...
Relation: Scientific Reports. 2019;9(1):20405; info:eu-repo/grantAgreement/ES/1PE/MTM2015-64465-C2-1-R; info:eu-repo/grantAgreement/EC/H2020/712949; Rodríguez-Morató J, Goday A, Langohr K, Pujadas M, Civit E, Pérez-Mañá C et al. Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity. Sci Rep. 2019;9(1):20405. DOI:10.1038/s41598-019-57002-9; http://hdl.handle.net/10230/43494; http://dx.doi.org/10.1038/s41598-019-57002-9
Rights: © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess
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