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The autophagy-lysosome pathway plays an essential role in promoting lipid catabolism and preventing hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). Transcription factor EB (TFEB) enhances the autophagy-lysosome pathway by regulating the expression of genes related to autophagy and lysosome biogenesis. Therefore, targeting TFEB provides a novel strategy for the treatment of lipid metabolic diseases. In this study, the antiallergic drug desloratadine was screened and identified as a novel TFEB agonist. Desloratadine effectively induced translocation of TFEB to the nucleus and promoted autophagy and lysosome biogenesis. Desloratadine-induced TFEB activation was dependent on AMPK rather than mTORC1. Moreover, desloratadine treatment enhanced clearance of lipid droplets in cells induced by fatty acids oleate and palmitate. Furthermore, high-fat diet (HFD) induced obesity mouse model experiments indicated treatment with desloratadine markedly reduced the body weight of HFD-fed mice, as well as the levels of hepatic triglycerides and total cholesterol, serum glutamic pyruvic transaminase and glutamic-oxaloacetic transaminase. Oil red O staining showed the liver fat was significantly reduced after desloratadine treatment, and H&E staining analysis demonstrated hepatocellular ballooning was improved. In addition, autophagy and lysosomal biogenesis was stimulated in the liver of desloratadine treated mice. Altogether, these findings demonstrate desloratadine ameliorates hepatic steatosis through activating the TFEB-mediated autophagy-lysosome pathway, thus desloratadine has an exciting potential to be used to treat fatty liver disease. [ABSTRACT FROM AUTHOR]

Imbalance of Th1/Th2 lymphocytes and cytokines is responsible for increasing rate of pathology, such as allergy, autoimmune processes and cancer. Pyrimidines have a wide spectrum of pharmacological activity, for example antiallergic properties. The aim of this study is to investigate effects of 5-hydroxypyrimidine derivatives on systemic anaphylaxis, concentrations of immunoglobulin E (IgE) and cytokines in comparison with Aerius in experiments on ovalbumin-induced systemic anaphylaxis model. Effects of 7-day course of intraperitoneal (i/p) administration of SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg, Aerius (i/p, 1.3 mg/kg) were studied in 140 male Balb/c ovalbumin-sensitized mice. 120 mice were immunized by two injections (two-week interval) of ovalbumin (100 mg per mouse) mixed with aluminum hydroxide (5 mg per mouse). 20 mice were used as intact control. Administration of SNK-411, SNK-578, or Aerius began after second immunization and lasted for 7 days. Within one hour after last injection of the compounds, 70 mice received injection of ovalbumin (100 mg dissolved in 0.1 mL saline) in retroorbital sinus. 70 mice from control and experimental groups were euthanized by decapitation. IgE, Interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-11, IL-17A, IL-17F, Interferon gamma (IFNγ), IL-13 concentrations were measured in blood sera. Administration of SNK-411, SNK-578 at the dose of 50 mg/kg decreased systemic anaphylaxis, lowered IgE concentration by 1.5-1.6 times compared to ovalbumin control group whereas Aerius did not reduce concentration of IgE. Administration of SNK-411, SNK-578 at 25 mg/kg, and 50 mg/kg, and Aerius decreased concentration of Th-2 cytokines (IL-4, IL-5, IL-13) compared to ovalbumin-treated control group. SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg increased level of IL-2. SNK-578 at 50 mg/kg increased concentration of IFNγ up to intact control level and decreased concentration of IL-6. 7-day administration of 5-hydroxypyrimidine derivatives at the dose of 50 mg/kg decreased severity of systemic anaphylaxis. SNK-411, SNK-578, Aerius lowered levels of proallergic cytokines in serum of sensitized mice. In contrast to Aerius, the 5-hydroxypyrimidine derivatives decreased serum IgE concentrations.

Introduction: For people with allergies, it is not always possible to prevent allergens admission to the body. For this reason, it is essential to create a long-acting drug that can prevent an allergic reaction. The very promising option is a transdermal therapeutic system (TTS), with H1 blockers. The aim of the study: To create a technology for the production of desloratadine-based TTS, suitable for routine use with prolonged drug releasing. Materials and Methods: Polyvinylpyrrolidone K30 (PVP) was used as the main matrix polymer for TTS, and the Kruofilm polymer membrane was used as the adhesive layer. The formation of the polymer membrane was carried out by drying a water-alcohol solution of the components at a temperature of 60ºC. Characterization of the obtained dosage forms was made by spectrophotometry. The resulting micelles size was measured by dynamic light scattering. Results and Discussion: Round shaped TTS (patches) with water-dissolved desloratadine (DL) and its micellar form were obtained. The size of micelles with DL was 22.8±5.2 nm. The spectrophotometric method for determining DL has been developed. The containing of DL in the patches ranged from 5 to 25 mg per patch, depending on the manufacturing technology. Conclusion: We have developed TTSs containing DL by a solution and a micellar form. A top adhesive layer has been selected that has moisture resistance, strength and reliable fixation of the matrix with the active substance on the skin. A method for the spectrophotometric determination of DL in solutions and patches was developed and validated.

Loratadine is metabolized to desloratadine. Both of them have been used for allergy treatment in children. Anatomical, physiological, and biological parameters of children and clearance of drugs vary with age. We aimed to develop a whole‐body physiologically based pharmacokinetic (PBPK) model to simultaneously predict the pharmacokinetics of loratadine and desloratadine in children. Following validation using 11 adult data sets, the developed PBPK model was extrapolated to children. Plasma concentrations following oral loratadine or desloratadine to children of different ages were simulated and compared with six children data sets. After scaling anatomy/physiology, protein binding, and clearance, pharmacokinetics of the two drugs in pediatric populations were satisfactorily predicted. Most of the observed concentrations fell within the 5th‐95th percentile range of the simulations in 1000 virtual children. The predicted area under the concentration‐time curve (AUC) and Cmax fell within 0.5‐2.0‐fold range of the observations. Oral doses of loratadine or desloratadine for children of different ages were simulated based on similar AUCs following 10 mg of loratadine or 5 mg of desloratadine for adults. Pediatric PBPK model was successfully developed to simultaneously predict plasma concentrations of loratadine and desloratadine in children of all ages. The developed pediatric PBPK model may also be applied to optimize pediatric dosage. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a common childhood disease. Although various drugs have been used to treat allergic rhinitis, including nasal corticosteroids, antileukotrienes, and antihistamines, there is still controversy about the optimal dose and the best combination with the highest efficacy. Higher doses of antihistamines are recommended for better control of urticaria, but there is insufficient evidence regarding the efficacy of increased doses of antihistamines in allergic rhinitis. The aim of the study was to evaluate the effectiveness of different drug combinations in the treatment of children with allergic rhinitis. Sixty-four children with persistent moderate to severe allergic rhinitis were enrolled and randomly divided into 4 groups. All children received mometasone furoate nasal spray once daily. In addition to mometasone, each group received one of the following drugs or drug combinations: daily desloratadine, twice daily desloratadine, montelukast, or a combination of desloratadine and montelukast. The severity of symptoms before and after the intervention was evaluated based on the total nasal symptoms score, including sneezing, nasal congestion, nasal itching, and rhinorrhea. Sixty patients completed the study. The reduction of nasal congestion score and total nasal symptoms score in the groups receiving desloratadine twice a day and desloratadine plus montelukast was superior to the daily desloratadine group and daily montelukast groups. According to this work, the treatment of allergic rhinitis with mometasone nasal spray with desloratadine twice a day or with the combination of desloratadine and montelukast was more effective than other treatment regimens. [ABSTRACT FROM AUTHOR]

Introduction: The application of double-J ureteral stents in urology is widespread, but their use is often accompanied by complications and bothersome symptoms, affecting patients' quality of life (QoL). While various medications have been tested for alleviating the symptoms associated with double-J stents, consensus on their effectiveness remains elusive. This study aims to investigate the effectiveness of tamsulosin, solifenacin, mirabegron, desloratadine, and combination therapy using a Romanian-adapted version of the Ureteral Stent Symptom Questionnaire (USSQ). Materials and Methods: A prospective, observational, randomised trial was conducted at the Urology and Renal Transplant Clinic of Dr. "C.I. Parhon" Clinical Hospital in Iasi between 1 January 2022 and 1 August 2023. Three hundred twenty seven patients who underwent their first double-J stent insertion were evaluated with the Romanian-adapted USSQ at baseline and 30 days post-insertion. Patients were randomly divided into six groups based on the prescribed medications: control, tamsulosin, mirabegron, solifenacin, desloratadine, and combination therapy. Results: The data suggest a significant reduction in symptoms in patients who received medication compared with the control group. Furthermore, the combined medication of solifenacin 10 mg and tamsulosin 0.4 mg was particularly effective in reducing pain with statistical significance compared to the control group (p = 0.001). The highest mean scores for urinary symptom severity were observed in the control group (12.37 ± 6.82), and the lowest was in the mirabegron group (9.94 ± 5.82). The individuals who received a daily dose of 50 mg of mirabegron saw the most notable influence on their job. Conclusions: While no single medication emerged as a "miracle drug" for managing symptoms related to double-J stent insertion, the combination therapy of solifenacin and tamsulosin is the most promising option for improving symptoms related to double-J stent insertion and QoL. Additional extensive research is required to validate these initial results. [ABSTRACT FROM AUTHOR]

Background: Our aim was to measure the effectiveness of oral isotretinoin with desloratadine compared with oral isotretinoin alone in treating moderate to severe acne at a tertiary care teaching hospital in North India. In this study, 90 patients with moderate to severe acne were enrolled to participate based on their fulfilling the inclusion criteria. Methods: A randomized, assessor‐blinded, parallel‐arm study was conducted. Randomization was done using computer‐generated tables to allocate treatments in a 1:1 ratio. A low‐dose oral isotretinoin at a dose of 0.3 mg/kg/day with tab desloratadine at 5 mg/day was applied to the study group and compared against the same patients going without the dosage when controls were conducted. Follow‐up was at 4, 8, and 12 weeks. Results: The primary outcome was an improved global acne grading system (GAGS) score and decreased acne lesion count. Secondary outcome: patient satisfaction with treatment. The 90 participants were randomized and 15 participants dropped out of the study, leaving 75 participants for intention to treat analysis (n = 41, n = 30). At week 12, the GAGS score and acne lesion count between the study and control groups were comparable (P > 0.05). Pruritus reported was 9.76% in the study versus 33.33% in the control group (P = 0.018). Also, 53.66% of participants reported "excellent" treatment satisfaction in the study group versus 36.67% in the control group. Conclusions: The addition of desloratadine to an isotretinoin regimen has a role in reducing disease and therapy‐related pruritus in acne and leads to improved patient satisfaction. [ABSTRACT FROM AUTHOR]

Introduction: For people with allergies, it is not always possible to prevent allergens admission to the body. For this reason, it is essential to create a long-acting drug that can prevent an allergic reaction. The very promising option is a transdermal therapeutic system (TTS), with H1 blockers. The aim of the study: To create a technology for the production of desloratadine-based TTS, suitable for routine use with prolonged drug releasing. Material and Methods: Polyvinylpyrrolidone K30 (PVP) was used as the main matrix polymer for TTS, and the Kruofilm polymer membrane was used as the adhesive layer. The formation of the polymer membrane was carried out by drying a water-alcohol solution of the components at a temperature of 60ºC. Characterization of the obtained dosage forms was made by spectrophotometry. The resulting micelles size was measured by dynamic light scattering. Results and Discussion: Round shaped TTS (patches) with water-dissolved DL and its micellar form were obtained. The size of micelles with DL was 22.8±5.2 nm. The spectrophotometric method for determining DL has been developed. The containing of DL in the patches ranged from 5 to 25 mg per patch, depending on the manufacturing technology. Conclusion: We have developed TTSs containing DL by a solution and a micellar form. A top adhesive layer has been selected that has moisture resistance, strength and reliable fixation of the matrix with the active substance on the skin. A method for the spectrophotometric determination of DL in solutions and patches was developed and validated. [ABSTRACT FROM AUTHOR]

Abstract In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.

Background and Aim: Allergic rhinitis is the most common atopic disorder and a chronic inflammatory disease of the airways, which can lead to disruption and decrease the patient's quality of life in the long term. This study was conducted to compare the effects of desloratadine and montelukast combined treatment with desloratadine monotherapy on clinical symptoms and quality of life of patients with persistent allergic rhinitis. Methods: This double-blind controlled clinical trial was conducted in the Ear, Nose and Throat Clinic of Metini Medical Training Center affiliated to Kashan University of Medical Sciences, on 56 patients with persistent allergic rhinitis. Patients were randomly assigned into two groups to receive combined treatment of montelukast (10 mg) and desloratadine (5 mg daily) or single drug treatment of desloratadine for a period of 6 weeks. At the beginning and end of the study, the quality of life and severity of clinical symptoms were evaluated by completing the miniRQLQ questionnaire and nasal symptom score in both groups. Results: In the intervention group (combined treatment of montelukast and desloratadine) and the control group (single drug treatment of desloratadine), the quality of life increased significantly after receiving the treatment compared to before (P

In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed. [ABSTRACT FROM AUTHOR]

To date, there has been a steady increase in allergic diseases, which is a heavy burden on the population and the health care system. The high prevalence, chronic course and pronounced impact on the quality of life require specialists to take a rational approach to the treatment of allergic pathology. From the moment of its appearance to the present, antihistamines have been widely used in real clinical practice, without losing their relevance. This article examines the place of antihistamines in modern therapy of the most common allergic and other histamine-dependent diseases.

Abstract Background Approximately 20–50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need. Methods RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs. Results We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC –PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation. Conclusions Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.