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.