Desloratadine Research Articles

Desloratadine via its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats

Background Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions. Objective DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats. Methods Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. Results Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed. Conclusion DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model wasestablished. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Microliquid/Liquid Interfacial Sensors: Biomimetic Investigation of Transmembrane Mechanisms and Real-Time Determinations of Clemastine, Cyproheptadine, Epinastine, Cetirizine, and Desloratadine.

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.

Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

In Vitro and In Vivo Characterization of the Transdermal Gel Formulation of Desloratadine for Prevention of Obesity and Metabolic Syndrome.

Chronic use of antihistamines can induce abnormalities in lipid absorption with potential excessive accumulation of lipids in the mesentery that can lead to the development of obesity and a metabolic syndrome. The focus of the present work was to develop a transdermal gel formulation of desloratadine (DES) to prevent/reduce obesity and metabolic syndromes. Nine formulations were prepared to contain hydroxypropyl methylcellulose (2-3%), DES (2.5-5.0%), and Transcutol® (15-20%). The formulations were evaluated for cohesive and adhesive properties, viscosity, drug diffusion through synthetic and pig ear skin, and pharmacokinetics in New Zealand white rabbits. Drug permeation was faster through the skin compared to synthetic membranes. The drug had good permeation, as indicated by very short lag time (0.08-0.47 h) and high flux (59.3-230.7 μg/cm2.h). The maximum plasma concentration (Cmax) and area under the curve (AUC) of transdermal gel formulations were 2.4 and 3.2 fold that of the Clarinex tablet formulation. In conclusion, as indicated by the higher bioavailability, transdermal gel formulation of DES may decrease the dose of the drug, compared to commercial formulation. It has the potential to reduce or eliminate metabolic syndromes associated with oral antihistamine therapy.

Ameliorative effect of desloratadine against cisplatin-induced renal and testicular toxicity in rats: Attention to TLR4/NLRP3 inflammasome signaling pathway

Cisplatin (CIS) is a potent anticancer drug that is used in the treatment of different types of cancer. Owing to its serious side effects, its clinical use is considerably limited. Aims: This study was mapped to investigate the potential effects of desloratadine (DES) against CIS-induced nephrotoxicity and testicular injury. Main methods: DES (5 and 10 mg/kg) was orally administered for 10 days, and CIS was injected once (10 mg/kg, i.p.) in adult male rats on day 9 to induce both renal and testicular toxicity. Key findings: DES significantly attenuated CIS-induced alterations in histopathology and biomarkers. DES resulted in a significant reduction in serum levels of creatinine (Cr), urea, and blood urea nitrogen (BUN), in addition to a marked decrease in urinary levels of albumin and total protein. Additionally, DES efficiently reinstated the oxidative balance by preventing the elevation of malondialdehyde (MDA) and enhancing superoxide dismutase (SOD) activity, and increasing glutathione (GSH) levels. Moreover, DES produced a profound decrease in renal and testicular levels of nucleotide-binding domain-(NOD) like receptor 3 (NLRP3), interleukin (IL)-1β, and caspase-1 when compared to the CIS group. Furthermore, DES significantly decreased CIS-induced elevation in toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) levels in both renal and testicular tissues. Significance: DES can be used as adjuvant therapy with CIS in cancerous cases, pending further clinical studies.

Investigation of the Antitumor Effects of Anti-inflammatory Desloratadine and Trimebutine on Different Types of Human Cancer Cells: An In Vitro study

Objective: Inflammation is a process associated with the development and progression of cancer. Desloratadine (DES) and Trimebutin (TMB) are anti-inflammatory agents used in the treatment of various diseases. This study aimed to investigate the antitumor effects of DES and TMB, which exhibit anti-inflammatory effects, on different human cancer cell lines. Materials and Methods: In this study, human prostate (LNCaP), ovarian (A2780), breast (MCF-7) and colon cancer (Caco-2) cell lines were treated with DES and TMB at concentrations of 1, 5, 25, 50 and 100 µM. Cells were treated with the compounds for 6, 12, and 24 hours, and the change in cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory concentration 50 (LogIC50) values of the compounds were calculated using GraphPad Prism 8 software based on cell viability results. The genotoxic effects of the compounds on cells were determined using the comet assay. Group comparisons were performed using the Kruskal-Wallis H test and p<0.05 was considered significant. Results: Exposure of LNCaP, A2780, MCF-7, and Caco-2 cells to DES and TMB agents for 6, 12 and 24 hours significantly reduced cell viability (p≤0.05). According to the comet assay results, DES and TMB caused significant DNA damage in the cell lines (p≤0.05). Conclusion: The study results demonstrate that DES and TMB, which have anti-inflammatory effects, exert cytotoxic effects by inducing DNA damage in cancer cells.

Effects of desloratadine on activated sludge: Behaviour of EPS and sludge properties

Desloratadine (DESL), a second generation of antihistamines, is an important anti-allergic pharmaceutical used to treat allergic rhinitis, hay fever and urticaria. In this study, the overall performance, extracellular polymeric substances (EPS) production, and sludge properties were assessed in a sequencing batch reactor wastewater treatment process with activated sludge during 139 days, under the presence of DESL (1, 5, and 10 mg L−1). DESL at 10 mg L−1 impacted biomass activity decreasing the chemical oxygen demand removal (78%) and the ammonium removal (71%). The removal of DESL was of 63%. Tightly bound EPS (TB-EPS) was significantly higher (149.5 mg gMLVSS−1) at the end of operation. Peaks attributed to protein-like fluorophores clearly predominated along the experimental phases using three-dimensional excitation-emission matrix (3D-EEM) fluorescence. The peak locations and intensities in the EPS fluorescence revealed the difference in the chemical structures of the EPS caused by DESL exposure. Quantitative image analysis results clearly demonstrated the formation of large aggregates. Principal component analysis (PCA) showed a positive relationship between TB-EPS components, and large aggregates. Moreover, the results allowed to distinguish the different operational phases, emphasizing the effect of DESL on EPS and aggregates.

FT-IR SPECTROSCOPIC APPROACH FOR THE QUANTITATIVE ANALYSIS OF FEW COMMERCIAL DRUGS IN BULK AND PHARMACEUTICAL FORMULATIONS

Simple, environment-friendly, rapid, accurate and cost effective Fourier Transform Infrared Spectroscopic (FT-IR) methods have been developed for the quantification of Bosentan (BSN), Desloratadine (DSD) and Flunarizine (FNZ) in bulk and marketed formulations. These drugs were estimated by several techniques and a new method has been developed by using FT-IR technique. The methods were developed on the basis of sample concentration influences the intensity of the vibrational bands and linearity is expected between concentration and optical density. The quantity of the drug present in commercial tablets with no interference of the excipients was estimated by applying this proposed method. This method has been validated in terms of LOD, LOQ, precision, accuracy, % RSD, robustness and ruggedness. A factor affecting the absorbance viz., concentration of drug is optimized. The presence of excipients has also been examined and found no significant effect. The calibration curves are found effective for the assessment of pure drug and pharmaceuticals. These curves also can be applied in bulk drug and pharmaceutical industries.

Effective RNAi in leukemia cells is enhanced by spermine-modified pullulan combined with desloratadine

RNA interference is a very useful tool for clinical treatment as well as mechanistic studies of leukemia. However, leukemia cells are known as hard-to-transfected by non-virus carriers. The low capacity of endocytosis and lysosomal escape of synthetic carriers are two obstacles for successful RNAi in leukemia cells. In this work, we established a universal powerful strategy for mediating effective RNAi in different types of leukemia cells by sequentially using spermine-modified pullulan (PS) as siRNA carrier and desloratadine (DL) to promote the lysosomal escape. It was shown that the complex of PS and siRNA could be largely internalized by human T-cell acute lymphoblastic leukemia cells, acute myeloid leukemia cells and chronic myeloid leukemia cells in serum-containing media, and the internalized complex was able to escape from the lysosomes by the aid of DL, resulting in effective RNAi against the key genes for the different leukemia cells.

An eco-friendly electrochemical process for the formation of a new desloratadine derivative and its antibacterial susceptibility. Report of a new type of ortho-quinhydrone complex

In this work, the synthesis of a new derivative of desloratadine (DQ-TBC complex) was carried out for the first time by a green electrochemical method. In order to create optimal conditions for the electrochemical synthesis of DQ-TBC complex, electrooxidation of 4‑tert-butylcatechol (TBC) was studied in the absence and presence of desloratadine (DES). To discover the reaction mechanism, the effects of solution pH, concentration of DES and potential scan rates were investigated using cyclic voltammetry and chronoamperometry techniques. The results suggest that the electrooxidation of TBC in the presence of DES leads to DQ through an ECE mechanism. This compound (DQ) is converted to the ortho-quinhydrone complex (DQ-TBC complex) as the final product after participating in a noncovalent interaction (hydrogen bonding) with TBC. The desired product was successfully synthesized in an ethanol/water mixture in a divided cell, at room temperature using carbon electrode (five ordinary soft carbon rods with total area 38 cm2) as the anode. The final product was identified by cyclic voltammetry, FTIR, NMR, Mass spectroscopic and thermogravimetric methods. Moreover, the synthesized compound was tested for antibacterial activity. The results indicated that DQ-TBC complex shows promising antibacterial activity against Bacillus cereus and Staphylococcus aureus, gram-positive bacteria.

Green potentiometric determination of some of the third-generation antihistamines: Fexofenadine, Desloratadine, and Levocetirizine by using new carbon paste electrodes

BackgroundThe Current study describes the construction of three carbon paste electrodes for the quantitative measurement of the third-generation antihistamines fexofenadine (FEX), Desloratadine (DES), and Levocetirizine (LEV). The different assembly steps of the sensor are described. The proposed potentiometric method Presents a green, fast, simple, and sensitive procedure for the determination of these drugs in their pure and pharmaceutical forms. ResultsThe quantitative determination of the antihistamines drugs was achieved using the constructed carbon paste electrodes. The presented analytical method obeyed linearity in the concentration range (5 × 10−6–1 × 10−2) M for FEX and DES, (1 × 10−5 – 1 × 10−2) M for LEV. The values of the Nernstian slopes (-57.40, -29.01, -56.01) mV/ decade indicate the closeness of these values from the ideal Nernstian slope value. The limits of quantification (LOQ) were (2.17 × 10−8- 6.31 × 10−8- 3.3 × 10−8) M, respectively. In addition, the electrodes exhibited good selectivity, repeatability (RSD<2%), stability, and fast response time. The method was validated and employed for the determination of the studied drugs in pharmaceutical dosage forms, the average recovery values were (99.13–99.53–99.90)% for FEX, DES, and LEV, respectively. ConclusionOur study included the construction of the first carbon paste electrodes for potentiometric determination of some of the third-generation antihistamines. The findings have shown that carbon paste electrodes excel over the traditional ion -selective electrodes and present an accurate, precise, green, robust, and cost-effective analytical method.

Surveillance of Stability Under Different Stress Conditions in Desloratadine and Study of Degradation Kinetics.

A stability-indicating method (SIM) stipulates the testing of the drug product and drug substances under the stressed conditions that will imply a clear notion about the stress conditions that would affect the drug in its finished dosage form. Furthermore, manufactures can clearly define the state at which the drug is unstable and present its storage conditions. The present article deals with the stability testing and degradation kinetic studies of desloratadine (DL). The method of analysis was UV visible spectroscopy, which is a most convenient and reliable method for the analyst. A method was developed and validated according to the ICH Q2 guidelines along with the amendment in 2018 (ICH Q14). The study denotes that the drug is extremely unstable in the presence of dry heat and then follows the oxidative and basic degradations. The acidic, neutral, and photolysis did not show notable degradations. The chemical kinetic studies were carried out to more clearly understand the mechanism of degradation and to present the order of reaction, rate of reaction, and reaction half-time. The application of a spectrophotometric method in the development of a SIM and study of degradation kinetics is much handier and cost-effective.

Simultaneous Determination of Loratadine and Its Metabolite Desloratadine in Beagle Plasma by LC-MS/MS and Application for Pharmacokinetics Study of Loratadine Tablets and Omeprazole‑Induced Drug-Drug Interaction.

BackgroundLoratadine (LTD) is a Biopharmaceutical Classification System II basic drug with pH-sensitive aqueous solubility and dissolution is a speed-limiting step of its absorption. The drug dissolution and the gastrointestinal tract pH conditions are likely to influence the in vivo pharmacokinetic behavior of LTD tablets.Materials and MethodA rapid, sensitive, and reliable bioanalytical method for simultaneous quantitation of LTD and its active metabolite desloratadine (DL) in beagle plasma was developed and validated based on liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation in low plasma consumption was accomplished by liquid–liquid extraction. The chromatographic separation was achieved on a Phenomenex Kinetex C8 column using acetonitrile and 5 mM ammonium formate as the mobile phase. A comparative pharmacokinetics study of three LTD tablets with different dissolution rates was conducted in male beagles in fasting state and an omeprazole-induced drug–drug interaction (DDI) study was subsequently performed under pretreatment of omeprazole.Results and ConclusionThe method showed a good linear correlation over the concentration ranges of 0.008–24 ng/mL for LTD and 0.8–800 ng/mL for DL, and was successfully applied to analyze the two compounds in beagle plasma. Pharmacokinetic results showed in the fasting state the three LTD tablets were equivalent in beagles in terms of effective components. DL of the three tablets were equivalent, indicating metabolite was less susceptible to pharmaceutic preparation factors for LTD tablets in beagles. Moreover, significant changes in LTD and DL pharmacokinetics parameters were observed under the effect of omeprazole-induced pH increase in gastrointestinal tract, suggesting that DDI effects are of concern for the curative effect of LTD when combined with omeprazole. The findings will contribute to the future pharmaceutical preparations research as well as the clinical application of LTD.

Comparison of efficacy and tolerability of oral desloratadine, rupatadine and ketotifen in seasonal allergic rhinitis

Rhinitis is inflammation of nasal mucosa which characteristically presents as running nose, blocked nose, itching on nose or sneezing. Allergic rhinitis is more common than non-allergic rhinitis. Anti-histamines are the mainstay of SAR treatment. Desloratadine, rupatadine and ketotifen are the commonly prescribed anti histamines in our region. In this study, we have compared efficacy and tolerability of desloratadine, rupatadine and ketotifen in SAR. This was a prospective, randomized, three arm, open label comparative study of desloratadine, rupatadine and ketotifen in SAR, conducted at Department of ENT, Kempegowda Institute of Medical Sciences, Bangalore; between January 2014 and December 2014. Patients’ severity of SAR symptoms were assessed by TNSS, QoL was measured using Medical Outcomes Study questionnaire (SF-12). SF-12 was administered at the start of study and then at the end of study. Adverse effects were monitored during clinical examination at each visit. Study subjects were systemically randomized into three groups – desloratadine (DES), rupatadine (RUP) and ketotifen (KET). Based on the assigned group; desloratadine was given orally in dose of 10mg OD, rupatadine orally 10 mg OD and ketotifen orally 1mg BD. All medications were given for 4 weeks. Follow up was done for all patients every week during treatment period of 4 weeks. The primary outcome measure was change in mean TNSS from baseline; secondary outcome measures were changes in the individual nasal symptom scores, change in the quality of life and tolerability to the study medications. Total 150 patients were recruited for this study, divided into 3 groups. DES and RUP were equally effective but significantly better than KET in improving rhinorrhea, nasal congestion, TNSS and AEC. (p=0.05). All the drugs were equally effective with no statistically significant intergroup difference in improving sneezing, nasal itching and QoL. RUP appeared to have better tolerability as the total number of adverse events were marginally less. DES and RUP are comparatively more effective and faster acting than KET. All the study medications were well tolerated with few mild, self-limiting, transient adverse events requiring no intervention.

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

IntroductionA small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure.ObjectiveThe aim was to study the association between DL exposure and incidence of first seizure.MethodsA new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001–2015 was conducted. DL exposure was defined as days’ supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure.ResultsA total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0–5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34–1.59). The aIRR ranged from 1.85 (95% CI 1.65–2.08) in children aged 0–5 years to 1.01 in adults aged 20 years or more (95% CI 0.85–1.19).ConclusionThis study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01106-7.

Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis

Currently, there is an urgent need to find a treatment for the highly infectious coronavirus disease (COVID-19). However, the development of a new, effective, and safe vaccine or drug often requires years and poses great risks. At this critical stage, there is an advantage in using existing clinically approved drugs to treat COVID-19. In this study, in vitro severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike pseudotyped viral infection experiments indicated that histamine H1 antagonists loratadine (LOR) and desloratadine (DES) could prevent entry of the pseudotyped virus into ACE2-overexpressing HEK293T cells and showed that DES was more effective. Further binding experiments using cell membrane chromatography and surface plasmon resonance demonstrated that both antagonists could bind to ACE2 and that the binding affinity of DES was much stronger than that of LOR. Molecular docking results elucidated that LOR and DES could bind to ACE2 on the interface of the SARS-CoV-2-binding area. Additionally, DES could form one hydrogen bond with LYS31 but LOR binding relied on non-hydrogen bonds. To our knowledge, this study is the first to demonstrate the inhibitory effect of LOR and DES on SARS-CoV-2 spike pseudotyped virus viropexis by blocking spike protein–ACE2 interaction. This study may provide a new strategy for finding an effective therapeutic option for COVID-19.

Synthesis of molecular-imprinting polymer coated magnetic nanocomposites for selective capture and fast removal of environmental tricyclic analogs

The organic residues of tricyclic analogs (TAA) in the environment such as cyproheptadine (CYP), amitriptyline (AMI), desloratadine (DES), 8-chloroazatadine (8-CHL), ketotifen fumarate (KF), and so on, brought many negative effects on human health. Hence, a novel magnetic molecularly imprinted polymers (MMIPs) combining magnetic Fe3O4 as the core with molecularly imprinted polymer using CYP as the template molecule, was successfully synthesized for highly selective capture and removal of TAA in water rapidly. CYP was selected as a template molecule, which was attributed to its representative structure among the five tricyclic analogues, and relatively inexpensive cost. The key preparation conditions were systematically optimized. The structure, morphology and adsorption behavior of MMIPs were studied in detail. The experimental results indicate that the prepared MMIPs possess high adsorption capacity, good selectivity, and fast reaction kinetics for tricyclic analogs. The maximum adsorption capacity of MMIPs for CYP, AMI, DES, 8-CHL, and KF is 48.89, 47.14, 47.33, 46.89, and 42.14 mg/g, respectively, which is significantly higher than that of magnetic non-molecular imprinting polymerizations because of the imprinting effect, with an imprinted layer thickness of approximately 10 nm. The imprinting factors of the synthesized materials are 4.74, 5.63, 5.69, 6.91, and 5.68, respectively. Meanwhile, the recovery rate of standard addition in environmental water samples is greater than 94.77%. Therefore, the synthesized MMIPs can be used as a promising material to capture and remove TAA in water selectively and quickly.

A promising approach to design thermosensitive in situ gel based on solid dispersions of desloratadine with Kolliphor® 188 and Pluronic® F127

Desloratadine (DSL) is an anti-allergic agent but its efficacy is limited with its low dissolution rate and aqueous solubility results in restricted bioavailability. The current study examines the probability of using Kolliphor® 188 (K188) and Pluronic® F127 (P127) as solubility improving agents of DSL that can be used to formulate in situ gel systems intended for nasal application in order to extend the contact time with nasal cavity and thereby maintain uptake of the drug. Solid dispersions (SDs) having various mass ratios of polymers and DSL were formulated using solvent-lyophilization method. SDs were evaluated for morphology, crystallinity, thermal behavior, solubility and dissolution rate to assess the efficiency of the polymers as solubility modifiers. SDs prepared with K188 and P127 demonstrated soft and fluffy structure, smaller particle size and narrower size distribution. DSC, FT-IR, 1H-NMR spectra confirmed the constitution of SDs and supplied information about the state of DSL in polymeric network. As the solubility of DSL was determined as 0.106 ± 0.009, all SDs prepared with K188 and P127 displayed enhanced solubility from 42- to 115-fold. Drug dissolution rate of DSL for all SDs was remarkably higher than of the pure DSL. K1 and P1 formulations were selected as optimum for designing nasal in situ gel systems. Gels designed by cold method were determined to show modified release fitted best to Peppas-Sahlin model. The transparent gels designed using sufficient quantities of polymers can be reducing the mucociliary clearance appear to be a feasible alternative to commercially available DSL tablets..

Evaluation of Thermal-Induced Polymorphic Transformation on Desloratadine and Desloratadine-Benzoic Acid Salt

Background: Active pharmaceutical ingredients face a challenge in manufacturing due to adverse physicomechanical properties. Desloratadine (DES) form I exhibits poor mechanical behavior through the formation of capping during the tableting process. Salt formation from DES and benzoic acid (BA) has been observed to resolve poor mechanical properties. However, the ability to withstand heat from the manufacturing process should be implemented in DES and DES-BA salt. The aim of this study was to determine the differences between thermal treatment results on DES and DES-BA salt and whether it causes them to undergo polymorphic transformation. Methods: Salt was crystallized between DES and BA using the solvent evaporation method. DES and DES-BA salt were heated at 110°C, 159°C (melting point of DES), 181°C (melting point of DES-BA), and 190°C. Following this, characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and solubility testing. Results: Polymorphic transformation caused by heat occurred in DES, but not in DES-BA salt. The transformation of DES was induced by the effect of heating, which changed polymorph I to a mixture of polymorph I and III at 110°C, to polymorph II at 159°C, and to a mixture of polymorph I, II, and III at 190°C. Under 190oC, DES-BA is still stable and did not undergo a polymorphic transformation. However, at 190oC, decomposition started to occur, which implied decreased solubility, which did not occur in DES. Conclusion: The heating process did not cause DES-BA salt to undergo a polymorphic transformation. However, it caused decomposition at 190oC. DES underwent a polymorphic transformation when exposed to the same condition without decomposition. This provided information to always pay attention to temperature during manufacturing processes that include DES or DES-BA salt to avoid physicochemical changes.