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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 -
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 -
Neurology India 2023
Topics: Humans; Domperidone; Proton Pump Inhibitors; Dopamine Antagonists; Parkinson Disease, Secondary
PubMed: 37148065
DOI: 10.4103/0028-3886.375378 -
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 -
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 -
Domestic Animal Endocrinology Apr 2023The scope of the present study is endocrine and metabolic control of sow lactation. This project aimed to determine the impact of increasing prolactin concentrations via...
The scope of the present study is endocrine and metabolic control of sow lactation. This project aimed to determine the impact of increasing prolactin concentrations via oral administration of the dopamine receptor antagonist domperidone in the first or third week of lactation in sows. Effects on sow hormonal and metabolic status, lactational performance, and gene expression in mammary epithelial cells were determined. Primiparous sows were divided in 3 treatments: 1) 10 mL of vehicle (table syrup) per os twice daily during the first and third weeks of lactation (Control, CTL, n = 23), 2) 0.5 mg/kg of domperidone per os twice daily during the first week of lactation (LACT1, n = 23), or 3) 0.5 mg/kg of domperidone given per os twice daily during the third week of lactation (LACT3, n = 22). Treated sows also received 10 mL of the vehicle twice daily during the other treatment period. Litter size was standardized to 12 ± 1 and piglets were weighed at birth, 24 h, and on d 8, 15, 22 (weaning), 35, and 56. Sow feed intake was recorded daily. Representative milk samples were obtained on d 7 and 21 of lactation for compositional analyses, and milk fat globules were used to measure mRNA abundances of various genes. Jugular blood samples were obtained from sows on d 1, 7, 14, and 21 of lactation to measure concentrations of prolactin, IGF-1, insulin, urea, and FFA. Concentrations of prolactin were increased (P < 0.01) at the end of the 7-d treatment period with domperidone, whether imposed in the first (LACT1) or third (LACT 3) week of lactation. No other blood variables were affected by treatments and neither was milk composition (P > 0.10). Sow BW, backfat thickness, or feed intake were not altered by treatments (P > 0.10), but piglet BW tended to be greater in litters from LACT3 compared with CTL sows on d 22 and 35 (P ≤ 0.10). Gene expression of EGF in milk fat globules tended to be (LACT1, P < 0.10) or was increased (LACT3, P < 0.05) after treatment, and the effect in LACT1 sows was maintained until d 21 of lactation. The mRNA abundance of SPP1 was increased (P < 0.05) in LACT1 vs CTL sows on d 7, and that of 3 major milk proteins tended to be (CSN1S2 and WAP, P < 0.10) or was greater (LALBA, P < 0.05) in LACT3 vs CTL sows on d 21 of lactation. Oral administration of domperidone during the first or third week of lactation increased prolactin concentrations and altered mRNA abundances of selected genes in milk fat globules. Yet, only the LACT 3 treatment positively affected piglet performance.
Topics: Animals; Female; Pregnancy; Administration, Oral; Animal Feed; Domperidone; Gene Expression; Lactation; Prolactin; RNA, Messenger; Swine; Weaning
PubMed: 37062172
DOI: 10.1016/j.domaniend.2023.106789 -
International Journal of Clinical... Jul 2023Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration approval of a new generic dry suspension formulation of domperidone by comparing the safety and pharmacokinetic profiles between the test and branded reference formulation in the context of fasted and fed condition.
MATERIALS AND METHODS
This was designed as a randomized, open-label, single-dose, two-period, two-treatment crossover study. 32 and 28 eligible healthy subjects were enrolled in the fasted and fed study, respectively. Each subject was randomly assigned to receive either the test or reference formulation in the first period, followed by a 1-week washout period and dosing of the alternate formulation in the second period. A series of blood samples were collected at scheduled timepoints within 48 hours after administration during each treatment period. Plasma concentrations of domperidone were determined by validated HPLC-MS/MS. Pharmacokinetic parameters, including C, t, AUC, AUC, and T, were acquired based on the concentration vs. time profiles by non-compartmental analysis using WinNonlin software. Then the geometric mean ratios (GMR) of C, AUC, and AUC between the two formulations and corresponding 90% confidence intervals (CIs) were calculated for bioequivalence determination. Safety was assessed as routine.
RESULTS
The two formulations showed similar pharmacokinetic profiles. Under fasted condition, the GMR and corresponding 90% CIs of AUC, AUC, and C were 101.48% (96.79 - 106.38%), 101.17% (96.66 - 105.90%), and 104.61% (96.73 - 113.14%), respectively. Under fed condition, the GMR and corresponding 90% CIs were 105.46% (99.19 - 112.12%), 104.21% (98.19 - 110.61%), and 112.78% (103.64 - 122.73%), respectively, for AUC, AUC, and C. All values fell within the accepted bioequivalence range of 80 - 125%. Both the test and the reference products were well tolerated without any serious or unexpected adverse reactions.
CONCLUSION
Pharmacokinetic bioequivalence was established between the two dry suspension formulations of domperidone in healthy Chinese subjects. Both products were safe and well tolerated.
Topics: Humans; Area Under Curve; Cross-Over Studies; Domperidone; East Asian People; Fasting; Healthy Volunteers; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 36999513
DOI: 10.5414/CP204309 -
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