-
Journal of Parkinson's Disease 2023Nausea is common upon initiating dopamine agonists in patients with Parkinson's disease (PD); however, pretreatment with an antiemetic is recommended only when...
BACKGROUND
Nausea is common upon initiating dopamine agonists in patients with Parkinson's disease (PD); however, pretreatment with an antiemetic is recommended only when initiating apomorphine formulations.
OBJECTIVE
Evaluate the need for prophylactic antiemetic use during dose optimization of apomorphine sublingual film (SL-APO).
METHODS
A post hoc analysis of a Phase III study evaluated nausea and vomiting treatment-emergent adverse events in patients with PD who underwent SL-APO dose optimization (10-35 mg; 5-mg increments) to achieve a tolerable FULL ON. Frequencies of nausea and vomiting were described for patients who did versus did not use an antiemetic during dose optimization and by patient subgroups based on extrinsic and intrinsic factors.
RESULTS
Overall, 43.7% (196/449) of patients did not use an antiemetic during dose optimization; most of these patients (86.2% [169/196]) achieved an effective and tolerable SL-APO dose. In patients who did not use an antiemetic, nausea (12.2% [24/196]) and vomiting (0.5% [1/196]) were uncommon. An antiemetic was used in 56.3% (253/449) of patients, with 17.0% (43/253) and 2.4% (6/253) experiencing nausea and vomiting, respectively. All events of nausea (14.9% [67/449]) and vomiting (1.6% [7/449]) were of mild-to-moderate severity except for 1 event each. Irrespective of antiemetic use, among patients without baseline dopamine agonist use, nausea and vomiting rates were 25.2% (40/159) and 3.8% (6/159); in those already using dopamine agonists, rates were 9.3% (27/290) and 0.3% (1/290).
CONCLUSION
Prophylactic treatment with an antiemetic is not necessary for most patients who initiate SL-APO for the treatment of OFF episodes in PD.
Topics: Humans; Antiemetics; Apomorphine; Dopamine Agonists; Nausea; Parkinson Disease; Vomiting
PubMed: 36970914
DOI: 10.3233/JPD-223537 -
Aquatic Toxicology (Amsterdam,... May 2023Domperidone is a dopamine D2 receptor inhibitor that stimulates pituitary gonadotropins. It is usually associated with synthetic GnRHa to promote spawning in fish....
Domperidone is a dopamine D2 receptor inhibitor that stimulates pituitary gonadotropins. It is usually associated with synthetic GnRHa to promote spawning in fish. However, the route of administration used, intramuscular injection, can be quite stressful. Little is known about the effects of domperidone, as well as other routes. This study aims to evaluate the toxicity of domperidone encapsulated by silica nanoparticles in zebrafish embryos. The study involved four groups with three concentrations: 1. domperidone (DP) 0.0001, 0.0002 and 0.0004 mg/mL; 2. DP associated with silica nanoparticles (SiNPs) 0.0001 + 1.1, 0.0002 + 2.2 and 0.0004 + 4.4 mg/mL; 3. SiNPs 1.1, 2.2 and 4.4 mg/mL and 4. Control (E3), with four repetitions per group. Survival, teratogen and heart rate (HR) were evaluated over a period of 168 hpf. Survival was higher in DP + SiNPs treatment, HR was lower in treatment with 4.4 mg/mL of SiNPs, while treatment with 0.004 mg/mL of DP increased HR. This study demonstrated that the association of DP and SiNPs decreased the toxicity of both DP and SiNPs, demonstrating that this may be a viable alternative to reduce the possible cardiotoxic effects of DP.
Topics: Animals; Zebrafish; Domperidone; Silicon Dioxide; Water Pollutants, Chemical; Nanoparticles
PubMed: 36958154
DOI: 10.1016/j.aquatox.2023.106454 -
Journal of Investigative Medicine : the... Jun 2023
Topics: Humans; Domperidone; Parkinson Disease; Gastrointestinal Diseases; Death, Sudden
PubMed: 36924398
DOI: 10.1177/10815589231161003 -
International Journal of Pharmaceutics Apr 2023An important feature of orodispersible tablets (ODTs) is the convenient administration of the drugs, in some cases, faster onset of action, stability maintenance, and...
An important feature of orodispersible tablets (ODTs) is the convenient administration of the drugs, in some cases, faster onset of action, stability maintenance, and dose precision. This work focused on the preparation of ODTs containing mannitol-based co-processed excipients Prosolv® ODT G2, Ludiflash® and Parteck® ODT in combination with tramadol, captopril, and domperidone by direct compression. Prosolv® ODT G2 showed high energy of plastic deformation due to the content of microcrystalline cellulose. Parteck® ODT provided compact tablets due to the content of granulated mannitol. All drugs decreased tensile strength, increased friability, prolonged disintegration time, and decreased the porosity of tablets. Tablets containing Prosolv® ODT G2 with captopril, domperidone, and tramadol; and Parteck® ODT with domperidone met the requirements for ODTs production, i.e., friability ≤ 1% and disintegration time ≤ 180 s, fast wetting time, high water absorption ratio, and adequate tensile strength. The disintegration time was tested using both the pharmacopeial method and the BJKSN-13 apparatus. The results indicate the significant difference between these methods, with the disintegration time being longer when tested with the BJKSN-13 instrument.
Topics: Excipients; Drug Compounding; Domperidone; Captopril; Tramadol; Administration, Oral; Solubility; Mannitol; Tablets
PubMed: 36921743
DOI: 10.1016/j.ijpharm.2023.122838 -
Alimentary Pharmacology & Therapeutics May 2023Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different... (Review)
Review
BACKGROUND
Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.
AIMS
Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?
METHODS
Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use.
RESULTS
Vomiting: Rationale for 5-HT , D , H or muscarinic antagonists, and mirtazapine, amitriptyline, nortriptyline, are poor. Arguments for inhibiting central consequences of vagal afferent transmission by NK antagonism are complicated by doubts over effects on nausea. Gastric emptying: Confusion emerges because of side-effects of drugs increasing gastric emptying: Metoclopramide (5-HT agonist, D and 5-HT antagonist; also blocks some emetic stimuli and causes tardive dyskinesia) and Erythromycin (high-efficacy motilin agonist, requiring low doses to minimise side-effects). Limited trials with selective 5-HT agonists indicate variable efficacy.
CONCLUSIONS
Several drug classes inhibiting vomiting have no scientific rationale. NK antagonism has rationale but complicated by limited efficacy against nausea. Studies must resolve variable efficacy of selective 5-HT agonists and apparent superiority over motilin agonists. Overall, lack of robust activity indicates a need for novel approaches targeting nausea (e.g., modulating gastric pacemaker or vagal activity, use of receptor agonists or new targets such as GDF15) and objective assessments of nausea.
Topics: Humans; Gastroparesis; Gastric Emptying; Motilin; Serotonin; Vomiting; Nausea
PubMed: 36919196
DOI: 10.1111/apt.17466 -
3 Biotech Apr 2023The current study is designed to evaluate the antiemetic effect of the diterpenoid phytol (PHY) using in vivo and in silico studies. For this, emesis was induced in...
The current study is designed to evaluate the antiemetic effect of the diterpenoid phytol (PHY) using in vivo and in silico studies. For this, emesis was induced in 4-day-old chicks by the oral administration of copper sulfate (CuSO.5HO) at 50 mg/kg. To see the possible antiemetic mechanism of PHY, we used a number of reference drugs such as domperidone (80 mg/kg), ondansetron (24 mg/kg) and hyoscine (100 mg/kg) as positive controls, while the vehicle served as a negative control group. PHY was administered orally at the doses of 50 and 75 mg/kg. Both PHY and reference drugs were given alone or in combined groups to evaluate their synergistic or antagonistic effects on the chicks. Molecular docking of PHY and reference drugs was carried out against 5HT, D, D, H, NK, and mAChRs (M-M) receptors for estimating binding affinity to the receptors. Drug-receptor interactions and active sites of the receptors were observed with the aid of different computational tools. The drug-likeness and pharmacokinetics of all the drugs were predicted through the SwissADME online database. The results suggest that PHY reduces the mean number of retches and increases latency dose-dependently in the birds. In the combination groups, PHY75 showed better antiemetic effects with domperidone and ondansetron. In addition, PHY exhibited the highest binding affinity with the D receptor (6CM4) (- 7.3 kcal/mol). In conclusion, PHY showed an antiemetic activity in chicks, possibly through the D receptor interaction pathway.
PubMed: 36919029
DOI: 10.1007/s13205-023-03520-3 -
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 -
International Journal of Molecular... Feb 2023Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the...
Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified. In the brain tissue, the expression levels of genes associated with schizophrenia were measured. The effects of DMP and morphine were compared to vehicle control and MK-801, a positive control to mimic schizophrenia. Gene expression analysis revealed that , , , , and th1 were up-regulated after 10 days of exposure to DMP and morphine, while was down-regulated. These two drugs also increased the number of positive dopaminergic neurons and the total dopamine level but reduced the locomotion and social preference. The termination of morphine exposure led to the up-regulation of , , and during the withdrawal phase. Our integrated data implicate that the dopamine system plays a key role in the deficits in social behavior and locomotion that are common in the schizophrenia-like symptoms and opioid dependence.
Topics: Animals; Calcium Channels; Dopamine; Dopaminergic Neurons; Morphine; Opioid-Related Disorders; Schizophrenia; Zebrafish; Domperidone; Dopamine Antagonists; Locomotion; Metabolic Networks and Pathways
PubMed: 36835497
DOI: 10.3390/ijms24044088 -
Drugs in Context 2023Proton-pump inhibitors, along with a prokinetic agent, are widely used to provide symptomatic relief amongst patients with acid peptic disease (APD). This article...
A real-world retrospective study of omeprazole-domperidone combination in managing acid peptic disease with PRoton-pump Inhibitors in patients with type 2 DiabEtes mellitus (PRIDE-2).
BACKGROUND
Proton-pump inhibitors, along with a prokinetic agent, are widely used to provide symptomatic relief amongst patients with acid peptic disease (APD). This article evaluates the effectiveness and safety of the omeprazole-domperidone combination amongst patients with type 2 diabetes mellitus for the management of APD.
METHODS
PRIDE-2 (PRoton-pump Inhibitor in patients with type 2 DiabEtes mellitus) is a retrospective study reviewing electronic medical records of patients with type 2 diabetes mellitus and APD who were receiving the omeprazole-domperidone combination and visiting multiple Indian healthcare settings between March 2018 and April 2021. The effectiveness outcome of the therapy was evaluated in terms of resolution of APD symptoms at visit 5 (120 days after baseline visit) compared with visit 1 (baseline visit). Safety was determined in terms of reported adverse events (AEs) during the treatment period (120 days).
RESULTS
A total of 174 patients were included in the study. The mean age of the patients was 51.5±9.6 years, with the majority (59.8%) being men. A significant proportion of patients reported relief from APD symptoms, including abdominal pain (91.6%), epigastric burning (68.7%), nausea (89.5%), flatulence (100.0%), loss of appetite (93.6%), and altered bowel movements (94.7%) (<0.001 for each) at visit 5 compared with visit 1. No serious AEs were reported.
CONCLUSION
Omeprazole-domperidone combination was beneficial in providing symptomatic relief to patients with diabetes and APD. The combination therapy was well tolerated, with few reports of minor AEs.
PubMed: 36816461
DOI: 10.7573/dic.2022-10-3 -
Current Drug Delivery 2024The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug...
BACKGROUND
The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs.
OBJECTIVE
This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and single-pass intestinal perfusion method.
METHODS
Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, . Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for single-pass intestinal perfusion investigations.
RESULTS
Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802 ± 0.418×10-4 cm/s).
CONCLUSION
To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.
Topics: Caco-2 Cells; Animals; Humans; Rats, Sprague-Dawley; Domperidone; Biological Availability; Permeability; Female; Rats; Administration, Oral; Intestinal Absorption; Emulsions; Drug Delivery Systems; Solubility; Particle Size; Intestinal Mucosa; Intestinal Barrier Function
PubMed: 36786136
DOI: 10.2174/1567201820666230214091509