TY - JOUR
T1 - Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity
AU - Rodríguez-Morató, Jose
AU - Goday, Albert
AU - Langohr, Klaus
AU - Pujadas, Mitona
AU - Civit, Ester
AU - Pérez-Mañá, Clara
AU - Papaseit, Esther
AU - Ramon, Jose Manuel
AU - Benaiges, David
AU - Castañer, Olga
AU - Farré, Magí
AU - de la Torre, Rafael
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/31
Y1 - 2019/12/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077183366&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-57002-9
DO - 10.1038/s41598-019-57002-9
M3 - Article
C2 - 31892725
AN - SCOPUS:85077183366
SN - 2045-2322
VL - 9
JO - SCIENTIFIC REPORTS
JF - SCIENTIFIC REPORTS
IS - 1
M1 - 20405
ER -
