Gastro-intestinal transit time
Besides the above-mentioned factors such as pH, gastric volume and gastric transition time, other factors like gastric emptying and gastro-intestinal transit time are relevant for absorption. After RYGB, a large proportion of the stomach and intestine is bypassed, which can result in altered gastro-intestinal transit time and gastric emptying time. Carswell et al. studied seven obese controls, six obese individuals undergoing adjustable gastric banding, seven subjects undergoing RYGB surgery, and five subjects undergoing biliopancreatic diversion with duodenal switch at 8 – 29 months post-surgery. The authors found no significant changes in gastro-intestinal transit time using a sulphasalazine/sulphapyridine test with sulphapyridine detected at 180 min in all four groups 31. Dirksen et al. measured the transit time of water and solid nutrients through the stomach, small intestine and colon through scintigraphy in 17 RYGB subjects who were at least 12 months post-surgery and in nine non-obese control subjects. In this study, RYGB subjects had faster pouch emptying for water as well for solid nutrients but slower small intestinal transit time and similar colonic transit time in comparison to healthy controls 32. Nguyen et al. studied the effect of RYGB on gastric emptying and cecal arrival time in ten RYGB subjects who underwent surgery at least 12 months earlier in comparison to healthy subjects 33. Compared to the healthy controls, gastric emptying and cecal arrival time were substantially faster in RYGB patients. Moreover, gastric emptying was faster when subjects were in a sitting position and tended to be faster after 150 ml in comparison to the 50 ml administration. Lastly, Wang et al. showed rapid gastric emptying in seven patients who underwent RYGB one year after surgery34, where the subjects were their own controls.
The results of these studies on gastric emptying and intestinal and colonic transit time show that gastric emptying is generally faster after bariatric surgery compared to healthy controls and that data on intestinal and colonic transit time is conflicting with more rapid and even slower small intestinal transit or cecal time reported in RYGB surgery patients.
Information on changes in the gastro-intestinal transit time as a result of bariatric surgery may also be deduced from results on studies evaluating the effect of bariatric surgery on the exposure of slow-release vs. immediate-release tablets. Yska et al. studied the effect of RYGB surgery on the exposure of metoprolol from immediate-release (IR) and controlled-release (CR) tablets in female patient volunteers one month before and six months after RYGB surgery35. The endpoint was the ratio of the metoprolol AUCafter/AUCbefore surgery. For the IR tablets, no significant changes were observed, albeit with major intraindividual and interindividual variability in AUC (range ratio AUC0–10 hours after/AUC0–10 hours before: 0.74–1.98). For the CR tablets, a significantly lower AUC was observed after surgery (range ratio AUC0–24 hours after/AUC0–24 hours before: 0.43–0.77). Based on these results, the authors conclude that RYGB surgery may influence the bioavailability of metoprolol from an IR tablet and that after surgery, the dose of metoprolol CR tablets should be increased according to clinical response 35. In contrast with these results, another study showed no significant effect on the AUC of metoprolol measured at 6 – 8 months after RYGB surgery in patients receiving oral metoprolol CR tablets 36. Also, for IR tablets, no changes in exposure after surgery were found. Because of differences in the volume of water used to swallow the CR tablet influencing pouch emptying and differences between women and men (Yska et al. only included female volunteers) as explanations for the diverging results for CR tablets, it seems yet too early for conclusions on the use of metoprolol CR tablets after surgery.
For venlafaxine administered as CR capsules, Krieger et al. showed no effect on AUC of venlafaxine and its primary metabolite 3-4 months after RYGB 37. Similarly, Hachon et al. investigated the effect of RYGB surgery on the pharmacokinetics of morphine CR tablets in RYGB patients (two years after surgery) and healthy controls. They found no significant changes in the AUC or other PK parameters between studied groups 38.
Based on the results of these studies on CR formulations, it seems that a priori, CR formulations may not need to be discouraged in patients after bariatric surgery.