Prokinetics Influence the Pharmacokinetics of Rabeprazole

Arai, Kumiko; Takeuchi, Yoji; Watanabe, Hideki; Tsukurimichi, A.; Uchida, Naoki; Imawari, Michio

doi:10.1159/000165351

Cited by 22 publications

(16 citation statements)

References 37 publications

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“…A recent study showed that promotion of gastric emptying with prokinetic agents increased the bioavailability of PPIs, which is related to their efficacy [63]. From these pharmacokinetic aspects, a question arises whether the delayed emptying during long-term PPI therapy may lower their therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review

2009

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The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.

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Section: Discussionmentioning

confidence: 99%

Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review

2009

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“…In other clinical studies, when a PPI (rabeprazole) was administered in combination with a prokinetic drug, the prokinetic enabled faster transit of the PPI from the stomach to the small intestine, which means that the higher PPI levels were in a stable state in the small intestine, significantly increasing the blood PPI concentration, and suggesting that prokinetics promote PPIs absorption. 16 Given this result, the prokinetic mosapride in the present study may also be responsible for the increased absorbance of the PPI esomeprazole, thereby enabling a more rapid initial improvement in the E+M group.…”

Section: Discussionmentioning

confidence: 66%

A Double-blind, Randomized, Multicenter Clinical Trial Investigating the Efficacy and Safety of Esomeprazole Single Therapy Versus Mosapride and Esomeprazole Combined Therapy in Patients with Esophageal Reflux Disease

Lee

Kim

Cho

et al. 2017

J Neurogastroenterol Motil

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Background/AimsWe aim to evaluate the efficacy and safety of combination therapy in erosive reflux disease (ERD) patients by comparing endoscopic healing rates according to the Los Angeles classification for esomeprazole alone, and esomeprazole plus mosapride. MethodsA total of 116 ERD patients were randomized to receive esomeprazole 40 mg once daily plus mosapride 5 mg 3 times daily (E+M group), or esomeprazole plus placebo (E only group) for 8 weeks. Patients recorded gastroesophageal reflux disease (GERD) symptom questionnaire at weeks 4 and 8. The primary endpoint was the endoscopic healing rate of ERD after 8 weeks of treatment. ResultsEndoscopic healing rates according to the Los Angeles classification was 32 (66.7%) in the E+M group and 26 (60.5%) in the E only group, but there was no statistically significant difference between the groups. Only at 4 weeks, the total GERD symptom score changes relative to the baseline significantly improved in the E+M group than that of the E only group (-13.4 ± 14.7 vs -8.0 ± 12.3, P = 0.041), and upper abdominal pain and belching score changes showed significantly improved in the E+M group than that of the E only group (P = 0.018 and P = 0.013, respectively). ConclusionsThe combination of a proton pump inhibitor with mosapride shows a tendency for upper abdominal pain, belching, and total GERD symptoms scores to improve more rapidly. This suggests that combination therapy with esomeprazole and mosapride will be useful for rapid improvement of specific GERD symptoms, such as upper abdominal pain and belching in ERD patients.

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“…31,32 The action mechanism of mosapride includes enhancement of esophageal motor function, acceleration of gastric emptying, and enhanced acid inhibitory effect of PPIs in humans. 23,[33][34][35] In this study, PPI treatment was associated with significant delays in gastric emptying by 53.9% prolongation in T 1/2 compared to baseline which was slightly higher than the previous report with 15-40% delay in T 1/2 during PPI treatment. 5,36 However, with mosapride added to PPI, the delayed gastric emptying did not occurr.…”

Section: Discussionmentioning

confidence: 53%