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Pharmaceutics May 2023Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose...
Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose significant administration challenges. In this study, we aimed to improve DOM solubility and avoid its metabolism by developing nanocrystals (NC) of DOM through a 3D printing technology-melting solidification printing process (MESO-PP)-to be delivered via a solid dosage form (SDF) that can be administered sublingually. We obtained DOM-NCs using the wet milling process and designed an ultra-rapid release ink (composed of PEG 1500, propylene glycol, sodium starch glycolate, croscarmellose sodium, and sodium citrate) for the 3D printing process. The results demonstrated an increase in the saturation solubility of DOM in both water and simulated saliva without any physicochemical changes in the ink as observed by DSC, TGA, DRX, and FT-IR. The combination of nanotechnology and 3D printing technology enabled us to produce a rapidly disintegrating SDF with an improved drug-release profile. This study demonstrates the potential of developing sublingual dosage forms for drugs with low aqueous solubility using nanotechnology and 3D printing technology, providing a feasible solution to the challenges associated with the administration of drugs with low solubility and extensive metabolism in pharmacology.
PubMed: 37242699
DOI: 10.3390/pharmaceutics15051459 -
Neurology India 2023
Topics: Humans; Domperidone; Proton Pump Inhibitors; Dopamine Antagonists; Parkinson Disease, Secondary
PubMed: 37148065
DOI: 10.4103/0028-3886.375378 -
BMC Nephrology May 2023Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients,...
BACKGROUND
Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients.
METHODS
This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant.
RESULTS
The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses.
CONCLUSION
The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.
Topics: Humans; Renal Insufficiency, Chronic; Glomerular Filtration Rate; Pakistan; Cross-Sectional Studies; Middle Aged; Anti-Bacterial Agents; Hypoglycemic Agents; Antihypertensive Agents; Kidney; Adult; Aged; Inappropriate Prescribing; Comorbidity; Diabetes Mellitus; Hypertension; Bacterial Infections
PubMed: 37127612
DOI: 10.1186/s12882-023-03167-5 -
Pharmaceuticals (Basel, Switzerland) Apr 2023BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their...
BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their bioavailability is using cyclodextrin-based nanosponges. This study aimed to optimise and evaluate the feasibility of a microwave-assisted approach to synthesise nanosponges and improve domperidone's solubility and drug delivery potential. In the production process, microwave power level, response speed, and stirring speed were optimised using the Box-Behnken approach. Ultimately, the batch with the smallest particle size and highest yield was chosen. The optimised method of synthesis of the nanosponges resulted in a product yield of 77.4% and a particle size of 195.68 ± 2.16 nm. The nanocarriers had a drug entrapment capacity of 84 ± 4.2% and a zeta potential of -9.17± 0.43 mV. The similarity and the difference factors demonstrated proof-of-concept, showing that the drug release from the loaded nanosponges is significantly greater than the plain drug. Additionally, spectral and thermal characterisations, such as FTIR, DSC, and XRD, confirmed the entrapment of the drug within the nanocarrier. SEM scans revealed the porous nature of the nanocarriers. Microwave-assisted synthesis could be used as a better and greener approach to synthesise these nanocarriers. It could then be utilised to load drugs and improve their solubility, as seen in the case of domperidone.
PubMed: 37111324
DOI: 10.3390/ph16040567 -
Cureus Mar 2023Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30%...
Introduction The global proton pump inhibitors (PPIs) market was valued at US$ 2.9 billion in 2020 and is expected to exhibit a compound aggregated growth rate of 4.30% during the forecast period (2020-2027), as they are regularly prescribed for many gastrointestinal disorders, and the treatment usually lasts for a longer period. PPIs are usually combined with antiemetics and prokinetic drugs. The price of PPIs for the same combination varies a lot, which can lead to a lot of financial burden on the patients. Objective To evaluate the cost ratio and percentage cost variation of commonly used PPIs in various combinations. Methodology The cost of different brands of commonly used PPIs in combination with other drugs was analyzed in our study. A total of 21 different combinations (10 capsules/tablets for oral use) were tabulated by referring to the "Monthly Index of Medical Specialities" October-December 2021, and 1mg online pharmacy. The cost ratio and percentage cost variation for various brands of a particular strength and dosage form were calculated and compared. Cost ratio > 2 and cost variation > 100% were considered significant. Results The results show a huge variation (1788.88%) in costs of different brands with the highest being rabeprazole 20 mg and domperidone 10 mg (cost ratio: 18.88, percentage cost variation: 1788.88%) in oral formulation, followed by pantoprazole 40 mg and itopride 150 mg. The minimum cost ratio (1.35) and percentage cost variation (1.35%) is for pantoprazole 40 mg and levosulpiride 75 mg. Logistic regression analysis between the number of brands and percentage cost variation gives an R value of 0.0923. Conclusion There is a wide variation in the prices of PPIs available in the market, which can inadvertently increase the financial burden of therapy on patients. Physicians need to be made aware of these price differences so that they can choose the best available alternative for patients, which can help in increasing compliance with the prescribed drugs.
PubMed: 37065352
DOI: 10.7759/cureus.36112 -
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 -
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