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Journal of Fluorescence May 2023This work demonstrates a simple and reliable HPLC method with fluorimetric detection for simultaneous estimation of domperidone (DOM) and naproxen (NAP). Successful...
This work demonstrates a simple and reliable HPLC method with fluorimetric detection for simultaneous estimation of domperidone (DOM) and naproxen (NAP). Successful chromatographic separation was accomplished using Inertsil ODS C18 column (5 μm, 4.6 × 150 mm) with gradient elution of the mobile phase consisting of 0.01 M phosphate buffer (pH 5.5) solution and acetonitrile. The gradient elution started with 25% acetonitrile increased linearly to 65% in 5 min, then kept at this percentage till the end of the run. The mobile phase was pumped at a flow rate of 1.0 mL/min. The excitation wavelength at 284 nm was found suitable for both DOM and NAP since it corresponds to a maximum for the minor component DOM and measurable excitation for NAP, while using 316 and 355 nm as emission wavelengths for DOM and NAP, respectively. Peaks eluted with excellent resolution at retention times 4.4 and 6.3 min for DOM and NAP, respectively. Performance of the proposed method was tested according to ICH guidelines in regard to linearity, ranges, precision, accuracy, robustness, detection and quantitation limits. Calibration curves were linear in the ranges of 0.8-3.6 and 1.0-2.5 µg/mL for DOM and NAP respectively with correlation coefficients not less than 0.9996. The validated method was successfully applied to the analysis of DOM and NAP in their laboratory prepared tablets resembling the commercial dosage form, and assay results were favorably compared with a published reference HPLC method. The method's greenness was assessed using the Analytical Eco-Scale and the novel Analytical Greenness metric (AGREE).
Topics: Domperidone; Naproxen; Chromatography, High Pressure Liquid; Tablets
PubMed: 36538143
DOI: 10.1007/s10895-022-03067-1 -
Indian Journal of Pharmacology 2022
Topics: Female; Pregnancy; Humans; Domperidone; Galactorrhea; Amenorrhea
PubMed: 36537410
DOI: 10.4103/ijp.ijp_351_22 -
Molecules (Basel, Switzerland) Nov 2022In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia...
In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia requirements. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were employed to explore the compatibility between Na-attapulgite and domperidone. The XRD and DSC show no interaction between the drug and Na-attapulgite. The FTIR spectrum indicates a shift in the absorption of N-H in the drug molecule, which can be explained by the hydrogen bonding interaction between the N-H in the DOM molecule and the -OH on the surface of Na-ATP. The diameter, hardness, friability and drug content of the tablets were measured, and they all met the relevant requirements of the United States Pharmacopoeia. In addition, the tablets with Na-attapulgite as excipient exhibit a better release performance within the release time of 12 h. These results demonstrate that the domperidone sustained-release tablets have been successfully prepared by using Na-attapulgite as an excipient. The doping of Na-ATP in domperidone sustained-release tablets improves the cytocompatibility. Moreover, with the increase of Na-ATP content, cells proliferate remarkably and cell activity is significantly enhanced.
Topics: Excipients; Domperidone; Delayed-Action Preparations; Technology, Pharmaceutical; Solubility; Tablets; Calorimetry, Differential Scanning; Powders; Spectroscopy, Fourier Transform Infrared; Adenosine Triphosphate
PubMed: 36500360
DOI: 10.3390/molecules27238266 -
Frontiers in Pharmacology 2022Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in "Synopsis of Golden Chamber" (Han Dynasty in the 3 century)...
Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in "Synopsis of Golden Chamber" (Han Dynasty in the 3 century) and the Zhizhu pill in "Differentiation on Endogenous" in Jin Dynasty (1,115-1,234). ZZKZ contains four botanical drugs, including L [Rutaceae; ], Koidz. [Compositae; ], DC [Apiaceae; ], and Bunge [Rosaceae; ], which have been widely used in clinical therapy for functional dyspepsia (FD). This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD. FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored. ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT receptor and increased 5-HT receptor mRNA expression in the guts of FD rats. This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT activity and increased 5-HT distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.
PubMed: 36467071
DOI: 10.3389/fphar.2022.1026660 -
Children (Basel, Switzerland) Nov 2022QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However,... (Review)
Review
QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, the interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neonates. Further research in this age category is needed to improve primary screening practices and QTcthresholds, earlier detection of risk factors and precision pharmacovigilance.
PubMed: 36421220
DOI: 10.3390/children9111771 -
Parasites & Vectors Oct 2022Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in...
BACKGROUND
Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function.
METHODS
This study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as "exposed" to or "infected" with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days).
RESULTS
Twenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 μg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 μg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0.
CONCLUSIONS
In this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD.
Topics: Animals; Dogs; Biomarkers; Diet; Dog Diseases; Domperidone; Leishmaniasis; Prospective Studies; Renal Insufficiency, Chronic
PubMed: 36316751
DOI: 10.1186/s13071-022-05537-8 -
The Journal of Biological Chemistry Dec 2022Cancer cells intrinsically proliferate in an autonomous manner; however, the expansion of cancer cell areas in a tissue is known to be regulated by surrounding...
Cancer cells intrinsically proliferate in an autonomous manner; however, the expansion of cancer cell areas in a tissue is known to be regulated by surrounding nontransformed cells. Whether these nontransformed cells can be targeted to control the spread of cancer cells is not understood. In this study, we established a system to evaluate the cancer-inhibitory activity of surrounding nontransformed cells and screened chemical compounds that could induce this activity. Our findings revealed that lonidamine (LND) and domperidone (DPD) inhibited expansion of oncogenic foci of KRASG12D-expressing transformed cells, whereas they did not inhibit the proliferation of monocultured KRASG12D-expressing cells. Live imaging revealed that LND and DPD suppressed the movement of nontransformed cells away from the attaching cancer cells. Moreover, we determined that LND and DPD promoted stress fiber formation, and the dominant-negative mutant of a small GTPase RhoA relieved the suppression of focus expansion, suggesting that RhoA-mediated stress fiber formation is involved in the inhibition of the movement of nontransformed cells and focus expansion. In conclusion, we suggest that elucidation of the mechanism of action of LND and DPD may lead to the development of a new type of drug that could induce the anticancer activity of surrounding nontransformed cells.
Topics: Domperidone; Indazoles; Antineoplastic Agents; Neoplasms; Animals; Mice; Epithelial Cells; Mammary Glands, Animal; Drug Screening Assays, Antitumor
PubMed: 36273581
DOI: 10.1016/j.jbc.2022.102635 -
Journal of Clinical Medicine Sep 2022The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are... (Review)
Review
Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO's International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.
PubMed: 36142915
DOI: 10.3390/jcm11185268 -
RSC Advances Aug 2022Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported... (Review)
Review
Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported so far. This review summarizes the synthetic strategies, synthetic routes and reaction processes of domperidone in detail. Domperidone can be synthesized from the coupling reaction of two benzimidazolone derivatives (intermediates 1 and 2). Intermediate 1 can be prepared by two synthetic routes: the cyclization of -phenylenediamine with carbonyl reagents followed by coupling with 1,3-dihalopropane, and the coupling reaction of o-halo or o-amino substituted nitrobenzene with 1,3-disubstituted propane followed by reduction and cyclization. The latter route avoids the production of di-substituted by-products and has higher reaction selectivity. Intermediate 2 is synthesized by coupling substituted nitrobenzene with 4-aminopiperidine followed by reduction and cyclization, which is similar to the synthetic route of intermediate 1. Understanding the advantages and drawbacks of these synthetic methodologies would provide insights for the development of new strategies to prepare domperidone. Moreover, the methods used to synthesize domperidone can provide alternative approaches in the preparation of drugs or compounds with similar structure.
PubMed: 36105951
DOI: 10.1039/d2ra03777g -
Cureus Aug 2022Acute gastroenteritis is one of the common diseases of childhood. Dehydration is the most frequent consequence of acute gastroenteritis, and vomiting is the most... (Review)
Review
Acute gastroenteritis is one of the common diseases of childhood. Dehydration is the most frequent consequence of acute gastroenteritis, and vomiting is the most distressing clinical manifestation. Various anti-emetic agents are used in practice to control vomiting. However, not all anti-emetic agents are safe and effective. This meta-analysis aims to compare the effectiveness of ondansetron and domperidone in the cessation of vomiting in children with acute gastroenteritis. The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy was developed to identify prospective studies that compared the effectiveness of ondansetron and domperidone in the cessation of vomiting in children with acute gastroenteritis. The primary outcome was the number of children in whom there was a cessation of vomiting. The secondary outcomes included a number of children who required an additional dose of the assigned anti-emetic and the number of children who required intravenous rehydration therapy. Overall, seven randomized trials were included in the current meta-analysis. The pooled sample size of enrolled patients was 1,262, of which 639 patients were randomized to the ondansetron group and 623 were randomized to the domperidone group. In the ondansetron group, a higher number of children experienced cessation of vomiting (risk ratio [RR]: 1.22, 95% CI: 1.08-1.37, p-value=0.002), a lower proportion of children needed an additional dose of the assigned anti-emetic (RR=0.50, 95% CI: 0.33-0.77, p-value=0.002), and a lower number of children received intravenous rehydration (RR: 0.37, 95% CI: 0.16-0.83, p-value=0.02) as compared to domperidone group. Compared to domperidone, ondansetron was found to have better efficiency in aiming cessation of vomiting in children with gastroenteritis.
PubMed: 36072202
DOI: 10.7759/cureus.27636