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Journal of Pediatric Gastroenterology... Aug 2023Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper... (Review)
Review
Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication ("off label") for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an "off label/on evidence" prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.
Topics: Infant; Humans; Child; Domperidone; Antiemetics; Gastrointestinal Diseases; Gastrointestinal Agents; Vomiting
PubMed: 37159421
DOI: 10.1097/MPG.0000000000003822 -
Journal of Human Lactation : Official... Aug 2023Induction of lactation in a non-gestational parent has numerous potential benefits including parent-child bonding, optimal nutrition, and health benefits to the child...
INTRODUCTION
Induction of lactation in a non-gestational parent has numerous potential benefits including parent-child bonding, optimal nutrition, and health benefits to the child and breast- or chest-feeding parent. For transgender women and nonbinary people on estrogen-based, gender-affirming hormone therapy, the ability to nourish their infants through production of their own milk may also be a profoundly gender-affirming experience. Two prior case studies have been published describing induced lactation in transgender women, but analysis of the nutritional quality of the milk produced has not been previously described.
MAIN ISSUE
Here we describe the experience of a transgender woman who underwent successful induction of lactation in order to breastfeed her infant, who was gestated by her partner.
MANAGEMENT
Through modification of exogenous hormone therapy, use of domperidone as a galactogogue, breast pumping, and ultimately direct breastfeeding, the participant was able to co-feed her infant for the first 4 months of life. We provide a detailed description and timeline of the medications used, laboratory and electrocardiographic measurements, results of the participant's milk analysis showing robust macronutrient content, and description of the participant's experience in her own words.
CONCLUSION
These findings provide reassurance about the adequacy of nutrition from human milk produced by non-gestational transgender female and nonbinary parents on estrogen-based, gender-affirming hormone therapy, and support the importance of this experience on a personal level.
Topics: Infant; Female; Humans; Breast Feeding; Transgender Persons; Lactation; Nutrients; Estrogens
PubMed: 37138506
DOI: 10.1177/08903344231170559 -
BMJ Open Oct 2023Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.
METHODS AND ANALYSIS
We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.
ETHICS AND DISSEMINATION
This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.
TRIAL REGISTRATION NUMBER
International Clinical Trial Registry Platform: NL9438.
Topics: Humans; Feasibility Studies; Fecal Microbiota Transplantation; Feces; Levodopa; Parkinson Disease; Pilot Projects; Prospective Studies; Treatment Outcome
PubMed: 37798034
DOI: 10.1136/bmjopen-2023-071766 -
Journal of Controlled Release :... Jul 2023The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of...
The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys. This N2B-system demonstrated a much greater formulation distribution ratio in the olfactory region in an in vitro experiment using a 3D-printed nasal cast and in vivo experiment using cynomolgus monkeys, as compared to that in other nasal drug delivery systems that comprise of a proprietary nasal powder device developed for nasal absorption and vaccination and a commercially available liquid spray. Additionally, Texas Red-labeled dextran (TR-DEX, 3 kDa) was administered using the N2B-system to estimate the drug transition pathway from the nasal cavity to the brain. TR-DEX preferentially localized to the olfactory epithelium and reached the olfactory bulb through the cribriform foramina. Moreover, domperidone, a model drug with poor blood-brain barrier permeability, was administered to assess the brain uptake of medicine after olfactory region-selective administration by using the N2B-system. Domperidone accumulation in the brain was evaluated using positron emission tomography with intravenously administered [F]fallypride based on competitive inhibition of the dopamine D2 receptor (D2R). Compared to other systems, the N2B-system significantly increased D2R occupancy and domperidone uptake in the D2R-expressing brain regions. The current study reveals that the olfactory region of the nasal cavity is a suitable target for efficient nasal drug delivery to the brain in cynomolgus monkeys. Thus, the N2B-system, which targets the olfactory region, provides an efficient approach for developing effective technology for nasal drug delivery to the brain in humans.
Topics: Humans; Animals; Administration, Intranasal; Powders; Domperidone; Macaca fascicularis; Brain; Drug Delivery Systems; Pharmaceutical Preparations
PubMed: 37315691
DOI: 10.1016/j.jconrel.2023.06.005 -
Biomolecules & Therapeutics Nov 2023The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2...
The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
PubMed: 37899746
DOI: 10.4062/biomolther.2023.173 -
Advances in Clinical and Experimental... Sep 2023Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover,...
BACKGROUND
Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate.
OBJECTIVES
The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment.
MATERIAL AND METHODS
We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3.
RESULTS
All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects.
CONCLUSION
Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure.
PubMed: 37665080
DOI: 10.17219/acem/171001 -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
The Journal of Maternal-fetal &... Dec 2023To assess whether oral domperidone compared to placebo increases the rate of exclusive breastfeeding for 6 months among post-lower segment cesarean section (LSCS)... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess whether oral domperidone compared to placebo increases the rate of exclusive breastfeeding for 6 months among post-lower segment cesarean section (LSCS) mothers.
METHODS
This double-blind Randomized Controlled Trial, conducted in a tertiary care teaching hospital in South India, included 366 post-LSCS mothers with delayed initiation of breastfeeding or with subjective feelings of not having enough milk. They were randomized to two groups - Group : Standard lactation counseling and oral Domperidone and : Standard lactation counseling and a placebo. The primary outcome was an exclusive breastfeeding rate at 6 months. Exclusive breastfeeding rates at 7 days and 3 months and serial weight gain of an infant were assessed in both groups.
RESULTS
Exclusive breastfeeding rate at 7 days was statistically significant in the intervention arm. The exclusive breastfeeding rates at 3 months and 6 months were higher in the domperidone arm compared to placebo but not statistically significant.
CONCLUSION
Oral Domperidone along with effective breastfeeding counseling showed an increasing trend of exclusive breastfeeding rate at 7 days and at six months. Appropriate breastfeeding counseling and postnatal lactation support are important in enhancing exclusive breastfeeding.
TRIAL REGISTRATION
The study was prospectively registered with CTRI - Reg no. CTRI/2020/06/026237.
Topics: Pregnancy; Infant; Humans; Female; Breast Feeding; Domperidone; Cesarean Section; Lactation; Cognition
PubMed: 36863712
DOI: 10.1080/14767058.2023.2185754