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Polymers Mar 2022In the present study, microcrystallinecellulose-colloidal silicon dioxide (MCC-SiO) and carboxymethylcellulose-colloidal silicon dioxide (CMC-SiO) conjugates have been...
In the present study, microcrystallinecellulose-colloidal silicon dioxide (MCC-SiO) and carboxymethylcellulose-colloidal silicon dioxide (CMC-SiO) conjugates have been investigated as superdisintegrants in fast dissolving tablets (FDTs). MCC-SiO and CMC-SiO conjugates were prepared and micromeritic studies, FTIR, SEM and XRD methods were utilized for characterizing the powdered conjugates. The conjugates were used for the preparation of domperidone FDTs by direct compression and the wetting time, water absorption ratio, disintegration time and in vitro drug release were evaluated. Effective pore radius of MCC-SiO and CMC-SiO conjugates for 1:1, 1:2.5 and 1:5 was found to be 13.35 ± 0.31 µm, 15.66 ± 0.17 µm and 18.38 ± 0.44 µm, and 16.81 ± 0.24 µm, 20.12 ± 0.39 µm and 26.37 ± 0.24 µm, respectively, compared to 12.21 ± 0.23 µm for MCC and 13.65 ± 0.21 µm for CMC. The results of effective pore radius indicate the wicking capability as well as the disintegration potential of MCC-SiO and CMC-SiO conjugates over pure MCC and CMC. The results of wetting time, water absorption ratio and disintegration time for MCC-SiO conjugates were found to be in the range of 19 ± 1.21 to 30 ± 1.33 s, 42 ± 0.28 to 49 ± 0.47% and 15 ± 2 to 40 ± 1 s, and for CMC-SiO conjugates were found to be in the range of 21 ± 1.13 to 40 ± 1.17 s, 42 ± 0.94 to 49 ± 0.57% and 12 ± 2 to 20 ± 3 s, respectively. Conjugation of MCC and CMC with SiO led to the formation of a complex with remarkable tablet superdisintegrant potential that could be used in preparing fast disintegrating tablets.
PubMed: 35267857
DOI: 10.3390/polym14051035 -
Frontiers in Pharmacology 2022Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid...
Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid (SXOL), have been recommended to alleviate dyspeptic symptoms. However, evidence of their safety and efficacy remains limited to date. AIM: To assess whether 2 weeks of therapy with SXOL was non-inferior to domperidone syrup in children with FD. In this randomized, double-blind, double-simulated, non-inferiority, multi-center clinical trial, we recruited children (3-14 years) with FD according to the Rome IV criteria from 17 tertiary medical centers across China. Patients were randomly allocated (1:1) to receive SXOL or domperidone syrup for 2 weeks. We compared the participants' clinical scores from both groups based on the severity and frequency of dyspepsia symptoms according to Rome IV criteria (0, 1, 2, and 4 weeks after randomization). The primary endpoint was the total response rate, which was defined as the proportion of patients with a decrease of 30% or more in the FD symptoms clinical score from baseline, at the end of the 2-weeks treatment. A non-inferiority margin of -10% was set. Secondary endpoints and adverse events were assessed. This trial is registered with www.Chictr.org.cn, number ChiCTR1900022654. Between February 2019 and March 2021, a total of 373 patients were assessed for eligibility, and 356 patients were enrolled and randomized. The clinical response rate at week two was similar for SXOL [118 (83.10%) of 142] and domperidone [128 (81.01%) of 158]; difference 2.09; 95% CI -6.74 to 10.71, thereby establishing non-inferiority. The total FD symptom scores were significantly improved in the two groups at 1-, 2-, and 4-weeks follow-up periods ( < 0.005). The decrease in symptom score compared with the baseline were similar between these two groups. Over the total study period, 10 patients experienced at least one treatment-related adverse event [six (3.37%)] in the SXOL group, four [(2.25%) in the domperidone group], although no serious adverse event was noted. Treatment with SXOL effectively improves dyspeptic symptoms and is well tolerated. In addition, it is not inferior to domperidone syrup and leads to sustained improvement in Chinese children with FD.
PubMed: 35185585
DOI: 10.3389/fphar.2022.831912 -
Cureus Jan 2022Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted...
Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.
PubMed: 35154966
DOI: 10.7759/cureus.20990 -
Pharmacoepidemiology and Drug Safety Jun 2022While the beneficial effects of medications are numerous, drug-drug interactions may lead to adverse drug reactions that are preventable causes of morbidity and...
PURPOSE
While the beneficial effects of medications are numerous, drug-drug interactions may lead to adverse drug reactions that are preventable causes of morbidity and mortality. Our goal was to quantify the prevalence of potential drug-drug interactions in drug prescriptions at Danish hospitals, estimate the risk of adverse outcomes associated with discouraged drug combinations, and highlight the patient types (defined by the primary diagnosis of the admission) that appear to be more affected.
METHODS
This cross-sectional (descriptive part) and cohort study (adverse outcomes part) used hospital electronic health records from two Danish regions (~2.5 million people) from January 2008 through June 2016. We included all inpatients receiving two or more medications during their admission and considered concomitant prescriptions of potentially interacting drugs as per the Danish Drug Interaction Database. We measured the prevalence of potential drug-drug interactions in general and discouraged drug pairs in particular during admissions and associations with adverse outcomes: post-discharge all-cause mortality rate, readmission rate and length-of-stay.
RESULTS
Among 2 886 227 hospital admissions (945 475 patients; median age 62 years [IQR: 41-74]; 54% female; median number of drugs 7 [IQR: 4-11]), patients in 1 836 170 admissions were exposed to at least one potential drug-drug interaction (659 525 patients; median age 65 years [IQR: 49-77]; 54% female; median number of drugs 9 [IQR: 6-13]) and in 27 605 admissions to a discouraged drug pair (18 192 patients; median age 68 years [IQR: 58-77]; female 46%; median number of drugs 16 [IQR: 11-22]). Meropenem-valproic acid (HR: 1.5, 95% CI: 1.1-1.9), domperidone-fluconazole (HR: 2.5, 95% CI: 2.1-3.1), imipramine-terbinafine (HR: 3.8, 95% CI: 1.2-12), agomelatine-ciprofloxacin (HR: 2.6, 95% CI: 1.3-5.5), clarithromycin-quetiapine (HR: 1.7, 95% CI: 1.1-2.7) and piroxicam-warfarin (HR: 3.4, 95% CI: 1-11.4) were associated with elevated mortality. Confidence interval bounds of pairs associated with readmission were close to 1; length-of-stay results were inconclusive.
CONCLUSIONS
Well-described potential drug-drug interactions are still missed and alerts at point of prescription may reduce the risk of harming patients; prescribing clinicians should be alert when using strong inhibitor/inducer drugs (i.e. clarithromycin, valproic acid, terbinafine) and prevalent anticoagulants (i.e. warfarin and non-steroidal anti-inflammatory drugs - NSAIDs) due to their great potential for dangerous interactions. The most prominent CYP isoenzyme involved in mortality and readmission rates was 3A4.
Topics: Aftercare; Aged; Anti-Inflammatory Agents, Non-Steroidal; Clarithromycin; Cohort Studies; Cross-Sectional Studies; Denmark; Drug Interactions; Drug Prescriptions; Female; Hospitals; Humans; Male; Middle Aged; Patient Discharge; Prevalence; Terbinafine; Valproic Acid; Warfarin
PubMed: 35124852
DOI: 10.1002/pds.5415 -
PloS One 2022Insufficient milk production is a common problem affecting breastfeeding women, in particular following Cesarean delivery. Wang Nam Yen herbal tea is a promising... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Insufficient milk production is a common problem affecting breastfeeding women, in particular following Cesarean delivery. Wang Nam Yen herbal tea is a promising traditional Thai medicine used by postpartum women to stimulate milk production, as an alternative to pharmaceutical galactagogues. We aimed to compare the efficacy of Wang Nam Yen herbal tea, domperidone, and placebo, in increasing milk production in mothers who underwent Cesarean delivery.
METHODS
Women who underwent uncomplicated cesarean delivery at Sunpasitthiprasong Hospital were randomized into three groups. The participants received the treatments daily for three consecutive days. The primary outcome was breast milk volume at 72 hours after delivery. Secondary outcomes were pregnancy and neonatal outcomes, adverse events, and participant satisfaction.
RESULTS
Of the 1,450 pregnant women that underwent cesarean delivery, 120 women were enrolled. Their mean age and gestational ages were 28.7 years and 38.4 weeks, respectively. Breast milk volume at 72 hours postpartum was significantly different among the three groups (p = 0.030). The post hoc Bonferroni correction indicated a significant difference in breast milk volume between Wang Nam Yen herbal tea group and placebo control group (p = 0.007) while there was no difference between Wang Nam Yen herbal tea group and domperidone group (p = 0.806) and between domperidone group and placebo control group (p = 0.018). There was no difference in pregnancy and neonatal outcomes, adverse events, and participant satisfaction among the three groups.
CONCLUSION
Wang Nam Yen herbal tea was effective in augmenting breast milk production at 72 hours postpartum in mothers following cesarean delivery, and there was no evidence that herbal tea and domperidone differed in terms of augmenting breast milk production.
TRIAL REGISTRATION
The study was approved by the institutional review board of Sunpasitthiprasong Hospital (No.061/2559) and was registered TCTR20170811003 with the Thai Clinical Trial Registry.
Topics: Adolescent; Adult; Cesarean Section; Domperidone; Female; Galactogogues; Humans; Lactation; Milk, Human; Placebo Effect; Postpartum Period; Pregnancy; Teas, Herbal; Treatment Outcome; Young Adult
PubMed: 35100251
DOI: 10.1371/journal.pone.0247637 -
Pharmaceuticals (Basel, Switzerland) Jan 2022Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches...
Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet's disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet's immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs.
PubMed: 35056125
DOI: 10.3390/ph15010069 -
Alcoholism, Clinical and Experimental... Mar 2022Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to...
BACKGROUND
Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol's effects on dopamine neurotransmission.
METHODS
Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment.
RESULTS
Domperidone attenuated ethanol's enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0 g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0 g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment.
CONCLUSIONS
These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.
Topics: Domperidone; Dopamine; Ethanol; Nucleus Accumbens; Ventral Tegmental Area
PubMed: 35040146
DOI: 10.1111/acer.14775 -
European Journal of Clinical... Apr 2022To describe drug utilisation patterns in neonatal units. (Observational Study)
Observational Study
PURPOSE
To describe drug utilisation patterns in neonatal units.
METHODS
Retrospective observational cohort study using data held in the National Neonatal Research Database (NNRD) for neonatal units in England and Wales including infants born at 23 to 44 weeks' gestational age (GA) from 01 January 2010 to 31 December 2017.
RESULTS
The cohort included 17,501 (3%) extremely preterm infants; 40,607 (7%) very preterm infants; 193,536 (31%) moderate-to-late preterm infants; and 371,606 (59%) term infants. The number of unique drugs received by an infant (median (IQR)) increased with decreasing GA: 17 (11-24) in extremely preterm, 7 (5-11) in very preterm, 3 (0-4) in moderate-to-late preterm, and 3 (0-3) in term infants. The two most frequently prescribed drugs were benzylpenicillin and gentamicin in all GA groups, and caffeine in extremely preterm. Other frequently used drugs among preterm infants were electrolytes, diuretics and anti-reflux medications. Among infants <32 weeks' GA, the largest increase in use was for surfactant (given on the neonatal unit), caffeine and probiotics, while domperidone and ranitidine had the largest decline.
CONCLUSION
Antibiotics, for all GAs and caffeine, among preterm infants, are the most frequently used drugs in neonatal medicine. Preterm infants are exposed to a high burden of drugs, particularly antibiotics. Changing patterns in use reflect the emergence of evidence in some areas but several non-evidence-based drugs continue to be used widely. Improvements are needed to ensure rational drug use on neonatal units.
REGISTRATION
ClinicalTrials.gov (NCT03773289). Date of registration 21 Dec 2018.
Topics: Cohort Studies; Drug Utilization; Gestational Age; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Intensive Care Units, Neonatal; Retrospective Studies; Wales
PubMed: 35028673
DOI: 10.1007/s00228-021-03267-x -
Chinese Medicine Dec 2021Prokinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an... (Review)
Review
BACKGROUND
Prokinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an effective and safe substitution. This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of different CHM formulae for FD against prokinetics.
METHODS
Seven international and Chinese databases were searched from their inception to July 2020 for randomised controlled trials (RCTs) on CHM versus prokinetics. Data from each RCT were first pooled using random-effect pairwise meta-analyses and illustrated as risk difference (RD) or standardised mean difference (SMD) with 95% confidence interval (CI). Random-effect NMAs were then performed to evaluate the comparative effectiveness of CHM formulae and displayed as RD with 95% CI or SMD with 95% credible interval (CrI). The GRADE partially contextualised framework was applied for NMA result interpretation.
RESULTS
Twenty-six unique CHM formulae were identified from twenty-eight RCTs of mediocre quality. Pairwise meta-analyses indicated that CHM was superior to prokinetics in alleviating global symptoms at 4-week follow-up (pooled RD: 0.14; 95% CI: 0.10-0.19), even after trim and fill adjustment for publication bias. NMAs demonstrated that Modified Zhi Zhu Decoction may have a moderate beneficial effect on alleviating global symptoms at 4-week follow-up (RD: 0.28; 95% CI: - 0.03 to 0.75). Xiao Pi Kuan Wei Decoction may have a large beneficial effect on alleviating postprandial fullness (SMD: - 2.14; 95% CI: - 2.76 to 0.70), early satiety (SMD: - 3.90; 95% CI: - 0.68 to - 0.42), and epigastric pain (SMD: - 1.23; 95% CI: - 1.66 to - 0.29). No serious adverse events were reported.
CONCLUSION
Modified Zhi Zhu Decoction and Xiao Pi Kuan Wei Decoction may be considered as an alternative for patients unresponsive to prokinetics. Confirmatory head-to-head trials should be conducted to investigate their comparative effectiveness against prokinetics.
PubMed: 34930390
DOI: 10.1186/s13020-021-00556-6 -
International Breastfeeding Journal Dec 2021Domperidone is the most frequently prescribed medicine used to increase breast milk supply. There is considerable controversy surrounding the use of domperidone in...
BACKGROUND
Domperidone is the most frequently prescribed medicine used to increase breast milk supply. There is considerable controversy surrounding the use of domperidone in lactation, due to limited evidence about efficacy and concerns about rare but life-threatening side-effects. Despite this, in many high-income settings such as Australia, use of domperidone among breastfeeding mothers appears to be increasing. The aim of this paper was to explore women's experiences of using domperidone during breastfeeding.
METHODS
Semi-structured interviews were conducted in 2019 with 15 women in Australia who reported using domperidone as a galactagogue during breastfeeding. Interviews were recorded, transcribed and analysed thematically.
RESULTS
Women reported a wide variety of practices concerning the timing of initiation of domperidone use, including prophylactic use, as well as the dose and duration of use. Prolonged periods of use and unsupervised dosing were commonly reported, these practices were sometimes associated with a fear of the consequences of stopping, insufficient provision of information about the drug or feeling dismissed by health professionals. Some women indicated that when doctors refused to prescribe domperidone they responded by doctor shopping and seeking anecdotal information about benefits and risks online, leading to unsupervised practices. Women often reported high expectations surrounding the effectiveness of domperidone, and most used the medication in conjunction with food/herbal galactagogues and non-galactagogue support. Positive outcomes following domperidone use included having greater confidence in breastfeeding and pride at achieving breastfeeding goals.
CONCLUSIONS
This study identified a variety of practices concerning domperidone use, including potentially unsafe practices, linked in some cases to inconsistent advice from health professionals and a reliance on online, anecdotal information sources. These findings emphasise the urgent need for development of clinical practice guidelines and a greater focus on translating existing evidence concerning domperidone into clinical practice, including clinical support that is tailored to women's needs.
Topics: Breast Feeding; Domperidone; Fear; Female; Galactogogues; Humans; Milk, Human
PubMed: 34886887
DOI: 10.1186/s13006-021-00438-5