Effect of Obesity and Roux-En-Y Gastric Surgery on Omeprazole Pharmacokinetics

Abstract

<b><i>Introduction:</i></b> The prevalence of obesity is increasing globally. The principal aim was to evaluate whether gastric bypass surgery modifies the bioavailability and pharmacokinetic (PK) parameters of omeprazole. <b><i>Methods:</i></b> Controlled, open-label, bioavailability clinical trial in patients undergoing Roux-en-Y gastric bypass (RYGB). Healthy patients with obesity (body mass index &#x3e;35) were included and assessed for omeprazole PKs before and after RYGB (1 and 6 months). PK sampling was done at baseline and several times up to 12 h after drug dosing. Pre- and post-surgery parameters were compared using paired ANOVA or Wilcoxon tests, and control versus cases using ANOVA or Mann-Whitney tests. Given the post-surgery change in body weight, parameters were corrected by dose/body weight. <b><i>Results:</i></b> Fourteen case and 24 control subjects were recruited; 92% were women (<i>N</i> = 35/38). In patients who underwent RYGB, maximum plasma concentration (<i>C</i>_max) was significantly reduced at 1 and 6 months after surgery compared with presurgery values (<i>p</i> = 0.001). Regarding the AUC, the values are lower at 1 and 6 months after surgery than at baseline (<i>p</i> &#x3c; 0.001). The drug clearance was also increased in the first month after surgery. No differences were found between patients 6 months after surgery and controls. <i>C</i>_max and AUC corrected by dose/body weight were significantly different between the baseline surgery subjects and controls. <b><i>Discusion/Conclusions:</i></b> Omeprazole bioavailability is reduced in patients with obesity at 1 and 6 months after RYGB. However, omeprazole PK parameters 6 months after RYGB are similar to control subjects, and thus no dose correction is required after RYGB for a given indication.