Impact of lubiprostone on gastric-emptying profile and the possible effect of concomitant domperidone in healthy adults
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BACKGROUND: Lubiprostone is effective for patients with chronic constipation. This agent sometimes causes upper gastrointestinal symptoms, such as nausea, which is one of the chief reasons for discontinuation. However, the etiology of and strategy against bothersome gastrointestinal symptoms of lubiprostone remain unclear. AIMS: The goal of this study was to investigate the influence of lubiprostone on the gastric-emptying profile of healthy adults. The effect of domperidone on gastric emptying and gastrointestinal symptoms after lubiprostone administration were also assessed. MATERIALS AND METHODS: 80 healthy male participants underwent 13C acetate breath testing to evaluate gastric emptying. The test meal comprised 200 kcal of a standard liquid nutrient. Each participant underwent 3 random breath tests with: 1) no premedication; 2) 24 µg of lubiprostone 30 minutes prior to the study; and 3) 24 µg of lubiprostone plus 10 mg of domperidone 30 minutes prior to the study. Gastrointestinal symptoms (heartburn, regurgitation, epigastric pain, fullness, distress feeling) during testing were evaluated using a 7-point scoring system. RESULTS: Gastric emptying was significantly delayed by the administration of lubiprostone. Among all 8 subjects, 4 reported heartburn after taking lubiprostone, whereas this symptom was not found when subjects received concomitant domperidone. However, gastric emptying showed little change between lubiprostone alone and lubiprostone plus domperidone. CONCLUSION: Lubiprostone delayed gastric emptying of liquid in healthy adults, which could be associated with the gastrointestinal symptoms caused by the agent. Domperidone seemed effective against such gastrointestinal symptoms after administration of lubiprostone. This effect seemed unrelated to gastric motility.
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Evaluation of domperidone efficacy to prevent aspiration pneumonia in patients with acute ischemic stroke: a randomized clinical trial.

BACKGROUND AND AIM: Aspiration pneumonia is an essential complication of acute ischemic stroke (AIS), which is responsible for increased three-fold mortality within a month. There is an interest towards the effect of prokinetics on prevention of stroke-associated pneumonia. The present study aimed to investigate the effect of domperidone to prevent pneumonia in patients with AIS. METHODS: In this randomized clinical trial, 150 patients with AIS were assigned to receive either domperidone 10 mg daily or placebo during hospitalization. The clinical outcomes including of aspiration pneumonia occurrence, gastrointestinal discomfort, the need for intensive care unit admission, the length of hospitalization, final mRs, and mortality were then evaluated in both groups. RESULTS: 150 [Mean age 67.5 ± 13.5 years, 90 men and 60 women] were randomized in a 1:1 ratio. Both groups were similar in terms of baseline characteristics. The domperidone group experienced significantly less dysphagia, nausea and vomiting, and aspiration pneumonia (P < 0.005). Although domperidone did not considerably reduce the mortality (P = 0.978), it resulted in lower mean mRS and shorter length of hospitalization (P < 0.001). CONCLUSION: Domperidone is an effective and well tolerated agent which could be considered as a promising agent to prevent stroke-associated pneumonia leading to a better clinical recovery.

Clinical and psychological assessment on xinwei decoction for treating functional dyspepsia accompanied with depression and anxiety.

The purpose of this study is to explore the psychological efficacy of Xinwei Decoction, a traditional Chinese herbal medicine, to treat functional dyspepsia (FD) accompanied with depression and anxiety. Seventy-three subjects, divided into three groups, had been given herbal medicine (Xinwei Decoction), prokinetic agent (Domperidone) and placebo, respectively for 8 weeks. Before and after treatment, all subjects were examined with FD symptom scale, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). As a result, the total scores of the three groups in FD symptom scale, HAMD and HAMA after treatment decreased in different levels, with the decrease in the herbal group more significant than the other two groups (p < 0.01), indicating the efficacy of the herbal medicine. The total effective rates of the herbal, Domperidone and placebo groups were 90%, 67% and 31%, respectively, which indicated significant effect differences between Xinwei Decoction and Domperidone (p < 0.05) and between Xinwei Decoction and placebo (p < 0.01), showing that the efficacy of herbal therapy was superior to that of the other two therapies. Furthermore, there was no one in the Domperidone and placebo groups being cured of depression and anxiety, while the curing rate in the herbal group was about 70%, indicating the efficacy of herbal medicine in comparison to that of Domperidone and placebo for anti-depression and anti-anxiety. The result demonstrated that Xinwei Decoction could not only alleviate FD symptoms but also relieve depression and anxiety.

Domperidone: review of pharmacology and clinical applications in gastroenterology.

Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Unlike metoclopramide, it does not cause any adverse neurological symptoms as it has minimal penetration through the blood-brain barrier. It thus provides an excellent safety profile for long-term administration orally in the recommended doses. Domperidone is widely used in many countries and can now be officially prescribed to patients in the United States by an investigational new drug application for the treatment of gastroparesis and any condition causing chronic nausea and vomiting. In view of this additional clinical exposure of domperidone to a new generation of gastroenterologists and other specialists, the purpose of this timely review is to revisit the pharmacology, clinical application, and safety profile of this beneficial medication.

Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers.

AIMS: To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. METHODS: Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. RESULTS: The pre-post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole -15.75 (-23.38, -8.13), combination -11.84 (-20.77, -2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F(3,45) = 8.39, P < 0.001), initial diameter of the light reflex response (F(3,42) = 3.78, P < 0.05), and light (F(3,45) = 5.21, P < 0.005) and dark (F(3,45) = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations. CONCLUSIONS: The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone had access to some central D2-receptors.

Evaluation of the combined effects of atropine and domperidone on the lower oesophageal sphincter.

The effects of sequential administration of both domperidone followed by atropine, and atropine followed by domperidone were examined on the lower oesophageal sphincter of 10 healthy volunteers. Domperidone, 10 mg, increased lower oesophageal sphincter pressure (LOSP) within 10 min of injection. Atropine, 0.6 mg given at the time of peak effect of domperidone, subsequently decreased LOSP. However, frequent measurement of LOSP during the succeeding 40 min demonstrated that LOSP did not decrease significantly below control levels during this drug sequence. When the drugs were administered in the reverse sequence, atropine, 0.6 mg, decreased LOSP within 5 min of injection and subsequent administration of domperidone, at the time of peak effect of the atropine, resulted in a gradual increase in LOSP. However, control values were not approached until 30 min had elapsed after the administration of the domperidone.