Development of fexofenadine self-microemulsifying delivery systems: an efficient way to improve intestinal permeability.

Aim: The present study aimed to prepare and evaluate fexofenadine self-microemulsifying drug-delivery systems (SMEDDS) formulation and to determine and compare its intestinal permeability using in situ single-pass intestinal perfusion (SPIP) technique. Methods: Fexofenadine-loaded SMEDDS were prepared and optimized. Droplet size, polydispersity index, zeta potential, drug release and intestinal permeability were evaluated. Results: Optimized formulation consisted of 15% oil, 80% surfactant and 5% cosolvent. Droplet size and drug loading of optimized formulation was 13.77 nm and 60 mg/g and it has released 90% of its drug content. Intestinal permeability of fexofenadine was threefold enhanced in SMEDDS compared with free fexofenadine. Conclusion: The results of our study revealed that SMEDDS could be a promising tool for oral delivery of fexofenadine with enhanced dissolution rate and intestinal permeability.

[Box: see text].

Establishment of a human nasal epithelium model of histamine-induced inflammation to assess the activity of fexofenadine as an inverse agonist and its link to clinical benefit.

Background: Fexofenadine (FEX) is an antihistamine that acts as an inverse agonist against histamine (HIS) receptor 1 (H1R), which mediates the allergic reaction. Inverse agonists may be more potent than neutral antagonists, as they bind the same receptor as the agonist (HIS) but stabilize the inactive form and induce an opposite pharmacological response, suppressing the basal activity of H1R and preventing HIS from binding. This study aims to establish and validate a model of HIS-induced inflammation based on fully reconstituted human nasal epithelial tissue to assess the activity of FEX as an inverse agonist in this model and explore its link to clinical benefit. Methods: The model was developed using nasal MucilAir™ (Epithelix) in vitro epithelium challenged by HIS. Two conditions were assessed in a side-by-side comparison: tissue was exposed to HIS + FEX with or without FEX pre-treatment (one-hour prior to HIS challenge). Tissue functionality, cytotoxicity, H1R gene expression, and inflammatory cytokines were assessed. Results: HIS at 100 µM induced significant 3.1-fold and 2.2-fold increases for inflammatory biomarkers interleukin (IL)-8 and IL-6, respectively (p < 0.0001), as well as rapid upregulation of H1R mRNA. Inflammatory biomarkers were inhibited by FEX and H1R expression was significantly reduced (p < 0.0001). FEX alone decreased H1R expression at all doses tested. With one-hour FEX pre-treatment, there was significantly higher downregulation of IL-8 (p < 0.05) and further downregulation of H1R expression and IL-6 versus without FEX pre-treatment; the effects of FEX were improved from 22% to 40%. Conclusion: A model of HIS-induced airway inflammation was established based on IL-8, IL-6 and H1R gene expression and was validated with FEX. FEX works as an inverse agonist, with a higher effect when used before+during versus only during the HIS challenge. Taking FEX before+during allergen exposure, or when symptoms first occur, may reduce basal activity and H1R gene expression, providing stronger protection against the worsening of symptoms upon allergen exposure.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Fexofenadine.

In this monograph, the potential use of methods based on the Biopharmaceutics Classification System (BCS) framework to evaluate the bioequivalence of solid immediate-release (IR) oral dosage forms containing fexofenadine hydrochloride as a substitute for a pharmacokinetic study in human volunteers is investigated. We assessed the solubility, permeability, dissolution, pharmacokinetics, pharmacodynamics, therapeutic index, bioavailability, drug-excipient interaction, and other properties using BCS recommendations from the ICH, FDA and EMA. The findings unequivocally support fexofenadine's classification to BCS Class IV as it is neither highly soluble nor highly permeable. Further impeding the approval of generic equivalents through the BCS-biowaiver pathway is the reference product's inability to release ≥ 85 % of the drug substance within 30 min in pH 1.2 and pH 4.5 media. According to ICH rules, BCS class IV drugs do not qualify for waiving clinical bioequivalence studies based on the BCS, even though fexofenadine has behaved more like a BCS class I/III than a class IV molecule in pharmacokinetic studies to date and has a wide therapeutic index.

Design of easily swallowable xerogel pill with enough physical strength through hardening-process under heating and humidification.

The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was double-structured small sphere composed of an inner drug core and an outer dried-gel layer, however, had problem of insufficient physical strength. In this study, it was attempted to use dextrin (DEX), one of oligosaccharides, to strengthen the xerogel pill. DEX was co-dissolved in the dropping fluid in the DFD process and co-loaded in the conventional pill, which was mainly composed of mannitol (MNT) as a filler, to prepare the rigid body. DEX-loaded pill could be successfully prepared with high recovery (>90 %) by optimizing the ratio of DEX and MNT. Further, the representative pills with and without DEX (P-DEX and P-MNT, respectively) were hardening-processed under humidification. The physical strength of P-DEX pill was significantly increased when humidified under severe condition, resulting in enough hardness (>5N) and friability (<1.0 %). Processed P-DEX was found to have dense structure covered with a thick outer shell, which would be formed by interparticle bridge of DEX. It was also found that processed P-DEX pill suppressed initial drug dissolution significantly and exhibited sustained dissolution behavior, suggesting the potential function of bitter taste masking. Processed P-DEX pill had excellent sliding behavior with low friction forces as a result of lubricant effect of xanthan gum (XG) surrounding the pills. Furthermore, the sliding test also suggested that processed P-DEX pill had hard candy-like texture, in contrast unprocessed P-DEX pill had orally disintegrating (OD) tablet-like texture. Various xerogel pills with such different swallowing texture would have a potential to accommodate the children's preferences when taking medication.

Designing and Synthesis of Novel Fexofenadine-Derived Hydrazone-Schiff bases as Potential Urease Inhibitors: In-Vitro, Molecular Docking and DFT Investigations.

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50=10.19±0.16 µM), 11 (IC50=15.05±1.11 µM), 10 (IC50=17.01±1.23 µM), 9 (IC50=17.22±0.81 µM), 13 (IC50=19.31±0.18 µM), and 14 (IC50=19.62±0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50=21.14±0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

Development and validation of an UPLC-MS/MS method for the simultaneous determination of fexofenadine and olmesartan in human serum: Application to in vivo pharmacokinetic studies.

A sensitive, reproducible, robust, high-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of fexofenadine and olmesartan in human serum. Samples (50 µL) undergo protein precipitation prior to UPLC-MS/MS analysis. The analytes were separated using an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 µm) at a flow rate of 0.5 mL/min using a gradient elution with a total run time of 4 min. The analytes were detected in positive ion mode and selected reaction monitoring (SRM) was used for quantitation. The standard curve concentration range was 1.0-500.0 ng/mL for both analytes and each analyte showed excellent linearity with correlation coefficients (R2 > 0.99). The intra- and inter-day accuracy and precision were ±15% for each analyte, and excellent recovery was demonstrated (93-98%) for both analytes. The method is well suited for high-throughput quantitative determination of fexofenadine and olmesartan simultaneously and was successfully applied to an in vivo pharmacokinetic and transporter phenotyping study in humans.

Fluorescence based methodology with greenness consideration for concurrent estimation of anti-allergic medication; application to dosage form.

A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.

A Perception-Based Survey on Practice Patterns Pertaining to the Diagnosis and Management of Allergic Rhinitis in India.

INTRODUCTION: Allergic rhinitis (AR) is increasingly prevalent in India, affecting a significant portion of the population and adversely impacting their quality of life. This nationwide survey aimed to explore the perceptions and clinical preferences of Indian physicians regarding the perceived prevalence, common symptoms, and various available treatments for AR. METHODS: This cross-sectional, observational, digital questionnaire-based survey was conducted from September 2022 to March 2023, involving physicians sharing insights on prevalence rates, diagnostic approaches, medication preferences, and immunotherapy practices in AR management. RESULTS: A total of 1608 physicians participated in this survey. The majority of physicians (n=684, 42.5%) reported that the prevalence of AR in routine clinical practice is between 21 and 40%. Physicians also noted a substantial burden of AR with asthma (n=626, around 40%). Total IgE count was reported as a mandatory test for the diagnosis of AR by 47.5% of physicians (n=764). For the management of mild cases of seasonal or perennial AR, 980 (60.9%) physicians preferred fexofenadine as an oral antihistamine of choice. Fluticasone furoate was the preferred intranasal corticosteroid (INCS) option (67.1% of physicians (n=1079)), for the management of patients with moderate to severe AR, the most recommended duration of INCS therapy was two to four months (40.9% of physicians). Doctors recommended a montelukast and antihistamine combination in mild AR (n=152, 9.5%), mild AR not responding to antihistamine alone (n=291, 18.1%), moderate to severe AR along with INCS (n=252, 15.7%), and AR with mild asthma (n=74, 4.6%). The majority of physicians (n=1512, 75.6%) preferred using fexofenadine in combination with montelukast for the management of AR. The majority of physicians (n=839, 52.2%) opined that the efficacy rate of oral montelukast-fexofenadine was 60-90% in the management of mild-moderate AR. Around 55.3% of physicians (n=889) had not used immunotherapy in their clinical practice. CONCLUSION: These observations offer a holistic view of how Indian physicians perceive the management of AR, a condition highly prevalent in India and often associated with asthma. It also highlights the treatment strategies employed in their day-to-day clinical practice.

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

An Evaluation of Wet Granulation Process Selection for API Prone to Polymorphic Form Conversion in the Presence of Moisture and Heat.

PURPOSE: Wet granulation (WG) is one of the most versatile processes to improve blend properties for processing. However, due to its need for moisture and heat, it is often considered not amenable to active pharmaceutical ingredients (APIs) prone to forming hydrates. Despite this claim, little literature exists evaluating the extent to which polymorphic form conversions occur for such API when processed with WG. This work sets out to explore two common WG methods, high-shear (HSG) and fluid-bed (FBG), and two drying processes, tray-drying (TD) and fluid-bed drying (FBD), and evaluate the risk they pose to hydrate form conversion. METHODS: The progression of anhydrous to hydrate form conversion of two model compounds with vastly different solubilities, fexofenadine hydrochloride and carbamazepine, was monitored throughout the various processes using powder X-ray diffraction. The resultant granules were characterized using thermogravimetric analysis, differential scanning calorimetry, BET adsorption, and sieve analysis. RESULTS: FBG and FBD processing resulted in the preservation of the original form of both APIs, while HSG+TD resulted in the complete conversion of the API. The FBD of fexofenadine and carbamazepine granules prepared with HSG resulted in partial and complete re-conversion back to the original anhydrous forms, respectively. CONCLUSION: The drying process is a critical factor in anhydrous form conservation. FBG and FBD yielded better preservation of the initial anhydrous forms. HSG could be an acceptable granulation method for API susceptible to hydrate formation if the API solubility is low. Selecting an FBG+FBD process minimizes API hydrate formation and preserves the original anhydrous form.

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.

Environmentally benign liquid chromatographic method for concurrent estimation of four antihistaminic drugs applying factorial design approach.

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.

Repurposing fexofenadine as a promising candidate for diabetic kidney disease: randomized clinical trial.

PURPOSE: Diabetic kidney disease (DKD) is a devastating complication of diabetes mellitus. Inflammation and histamine are potentially involved in the disease progression. This study aimed to evaluate the role of fexofenadine in patients with DKD. METHODS: From January 2020 to February 2022, out of 123 patients screened for eligibility, 61 patients completed the study. Patients were randomized into two groups, the fexofenadine group (n = 30): received ramipril plus fexofenadine, and the control group (n = 31): received ramipril only for six months. Changes in urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were considered primary outcomes. Measurements of urinary cyclophilin A, monocyte chemoattractant protein-1 (MCP-1), 8-hydroxy-2' deoxyguanosine (8-OHdG), and podocalyxin (PCX) were considered secondary outcomes. The study was prospectively registered on clinicaltrial.gov on January 13, 2020, with identification code NCT04224428. RESULTS: At the end of the study, fexofenadine reduced UACR by 16% (95% CI, - 23.4% to - 9.3%) versus a noticeable rise of 11% (95% CI, 4.1% to 17.8%) in UACR in the control group, (p < 0.001). No significant difference in eGFR was revealed between the two groups. However, the control group showed a significant decrease of - 3.5% (95% CI, - 6.6% to - 0.3%) in eGFR, compared to its baseline value. This reduction was not reported in the fexofenadine group. Fexofenadine use was associated with a significant decline in MCP-1, 8-OHdG, and PCX compared to baseline values. CONCLUSION: Fexofenadine is a possible promising adjuvant therapy in patients with DKD. Further large-scale trials are needed to confirm our preliminary results.

Solubility enhancement of fexofenadine using self-nano emulsifying drug delivery system for improved biomimetic attributes.

BACKGROUND: Fexofenadine is a poorly water-soluble drug, which limit its bioavailability and ultimately therapeutic efficacy. Liquid self-nano emulsifying drug delivery system (L-SNEDDs) is an approach that can enhance the solubility of fexofenadine by increasing its surface area and reducing the particle size, which increases the rate and extent of drug dissolution. METHOD: In this investigation, L-SNEDDs of fexofenadine was made up using surfactants and co-surfactant. The SNEDDS formulation was optimized using a pseudo-ternary phase diagram and characterized. RESULTS: The optimized L-SNEDDS incorporated fexofenadine were thermodynamically stable and showed mean droplet size and zeta potential of 155nm and -18mV, respectively unaffected by the media pH. In addition, the viscosity, and refractive index were observed 18.4 and 1.49 cps, respectively for optimized L-SNEDDS fortified fexofenadine. The results of Fourier transform infrared spectroscopy revealed an insignificant interaction between the fexofenadine and excipients. A drug loading efficiency of 94.20% resulted with a complete in vitro drug release in 2h, compared with the pure drug, which demonstrate significant improvement in the efficacy. Moreover, these results signify that on further in vivo assessment L-SNEDDS fortified fexofenadine can indicate improvement in pharmacokinetic and clinical outcome. CONCLUSION: Thus, the investigation revealed that, the L-SNEDDs incorporated fexofenadine was most effective with a mixture of surfactant and co-surfactant with improved solubility intend to relieve pain associated with inflammation with single-dose oral administration.

Comparison of the efficacy of combined budesonide and fexofenadine versus combined fluticasone propionate and fexofenadine on the expression of class-4 semaphorins and their receptors in the peripheral blood cells of patients with allergic rhinitis.

Background: Allergic rhinitis (AR) is a common immunoglobulin (Ig) E-mediated disease. This study aimed to evaluate the gene expression levels of class 4 semaphorins and their receptors in AR patients before and after treatment with budesonide and fexofenadine (B/F) compared to fluticasone propionate and fexofenadine (FP/F). Methods: In this study, 29 AR patients (age 34.4 ± 1.2 years, 18 men and 11 women) were treated with B/F, and 24 AR patients (age 32.8 ± 1.9 years, 15 men and 9 women) were treated with FP/F for one month. Before and after treatment, peripheral blood samples were taken from patients. The expression levels of SEMA4A, SEMA4C, SEMA4D, Plexin-B2, and Plexin-D1 genes were measured using the qPCR method. In addition, the serum levels of IgE were measured using an enzyme-linked immunosorbent assay (ELISA). Results: The expression levels of SEMA4A (P = 0.011), 4C (P = 0.017), Plexin-B2 (P = 0.0005), and Plexin-D1 (P = 0.008) remarkably increased in AR patients treated with B/F. Our results show a significant reduction in the gene expression levels of SEMA4A (P = 0.002), 4C (P = 0.014), 4D (P = 0.003), Plexin-B2 (P = 0.033), and Plexin-D1 (P = 0.035) after treatment with FP/F. The serum levels of IgE increased in FP/F treated group (P = 0.017) and conversely decreased in the treated group with B/F (P = 0.019). Moreover, the percentages of eosinophils were reduced in both FP/F and B/F groups (P = 0.015 and P = 0.0001, respectively). Conclusion: In conclusion, concomitant use of fexofenadine and fluticasone propionate reduced SEMA4A, 4C, 4D, Plexin-B2, and Plexin-D1, while the SEMA4A, 4C, Plexin-B2, and Plexin-D1 gene expression levels were increased in the patient group treated with B/F.

Eco-friendly synchronous fluorescence spectrofluorimetric method for simultaneous determination of montelukast sodium and fexofenadine hydrochloride in their antiallergic rhinitis fixed-dose combination tablets.

An innovative, simple, accurate, sensitive, and eco-friendly synchronous fluorescence spectrofluorimetric method has been developed for the simultaneous analysis of montelukast sodium (MON) and fexofenadine hydrochloride (FEX). The method relies on measuring the relative synchronous fluorescence intensity of both drugs using Δλ of 60 nm in methanol at 405 nm for MON and 288 nm for FEX. The experimental parameters influencing the developed method were investigated and optimized. The method was linear over the ranges 0.1-2.0 and 2.0-20.0 µg/ml for MON and FEX, respectively. The limits of detection were 0.018 and 0.441 µg/ml, and the limits of quantitation were 0.055 and 1.336 µg/ml for MON and FEX, respectively. The developed method was applied successfully for the determination of the two drugs in their newly released fixed-dose combination prescribed for the treatment of allergic rhinitis. The mean per cent recoveries were found to be 100.680 ± 0.890 and 100.110 ± 0.940 for MON and FEX, respectively. Furthermore, the method was found to be eco-friendly green as was evaluated according to the Green Analytical Procedure Index tool guidelines and analytical eco-scale.

Bioequivalence of 2 Pediatric Formulations of Fexofenadine Hydrochloride Oral Suspension.

Fexofenadine hydrochloride (HCl) is a second-generation, nonsedating, histamine H1-receptor antagonist used to manage seasonal allergic rhinitis and chronic idiopathic urticaria. A new oral pediatric suspension of fexofenadine HCl has been developed, with the preservative potassium sorbate replacing parabens. The objective of this phase 1 single-center, open-label, randomized, 2-treatment, full-replicated, 4-period, 2-sequence crossover study in healthy adult volunteers was to assess the bioequivalence of 30 mg of the new oral suspension of fexofenadine HCl (test) versus 30 mg of the marketed pediatric oral suspension of fexofenadine HCl (reference). The replicate design was based on the high intra-individual variability of fexofenadine (>30% on Cmax ). The study comprised 68 randomized and treated volunteers. Plasma concentrations of fexofenadine were similar following the administration of a single dose of each formulation. Cmax , AUClast , AUC, median tmax , and mean t1/2z were similar between administrations of the same fexofenadine formulation and between formulations. A high intra-individual variability was confirmed with both formulations. Bioequivalence of the test and reference fexofenadine HCl formulations was demonstrated as the 90% confidence intervals of the geometric least squares mean ratio for Cmax , AUClast , and AUC of fexofenadine were all within the bioequivalence range of 0.80-1.25. There were no serious adverse events (AEs) or study discontinuations due to treatment-emergent AEs with either fexofenadine HCl formulation. The new paraben-free fexofenadine HCl 30-mg oral suspension and marketed fexofenadine HCl 30-mg pediatric oral suspension are bioequivalent under fasting conditions, with no safety concerns and a safety profile consistent with the known profile of fexofenadine.

P-glycoprotein mechanical functional analysis using in silico molecular modeling: Pharmacokinetic variability according to ABCB1 c.2677G > T/A genetic polymorphisms.

P-glycoprotein (P-gp) is a widely membrane-expressed multi-drug transporter. It is unclear whether the pharmacokinetic diversity of P-gp substrates is highly dependent on ABCB1 polymorphisms encoding P-gp. The purpose of this study is to analyze the mechanistic function of P-gp through in silico molecular modeling and to approach the resolution of controversy over pharmacokinetic differences according to ABCB1 polymorphisms. P-gp conformations of apo, ligand-docked, and outward-facing states can be modeled based on structural information of human P-gp. And polymorphic P-gp structures were constructed through homology modeling. ABCB1 c.2677G > T/A (Ala893Ser/Thr), did not correspond to P-gp's nucleotide-binding-domain (NBD) or drug-binding-pocket (DBP) or involve mechanical conformational changes. Although amino acid substitution by ABCB1 c.2677G > T/A caused a 30 % increased strain in an α-helix hinge between the NBD and DBP in P-gp's internal tunnel, there were no overall structural changes compared to wild-type. ABCB1 c.2677G > T/A may increase torsional energy, impacting conformational change rate, but this does not significantly affect P-gp's general functioning. Fexofenadine docking into P-gp's DBP explained the substrate interaction, but no effect by ABCB1 c.2677G > T/A was confirmed. Our findings provide additional insights useful in resolving the debate about the influence of ABCB1 polymorphisms on the interindividual pharmacokinetic variability of P-gp substrates.

Update meta-analysis on the efficacy and safety issues of fexofenadine.

Background: Fexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. Methods: Double blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. Results: From the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) -0.33; 95% CI-0.47 to -0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to -0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88-1.21), with no detection of heterogeneity across these 12 studies. Conclusions: According to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.

The efficacy of a combination of naproxen and fexofenadine (SJP - 002) to inhibit the symptoms that are associated with viral upper respiratory tract infection: Four case reports of individuals with common cold.

Key Clinical Message: There is no effective treatment that reduces both the severity and duration of a common cold episode. SJP - 002 (naproxen and fexofenadine) reduced symptom severity by two-third, and the duration of the common cold episode approximately by half. Abstract: The common cold is one of the most frequently experienced immune-related complaints. At present, available treatments have limited efficacy in inhibiting symptoms associated with upper respiratory tract infection, nor do they significantly shorten the duration of common cold episodes. Four case reports are presented of individuals with a common cold. Three of them self-administered the combination of naproxen and fexofenadine (SJP - 002). Results of one individual were compared to her spouse, who did not take SJP - 002 to treat common cold, while two other individuals took SJP - 002 and compared symptom severity with another common cold episode they experienced previously without taking SJP - 002. SJP - 002 reduced the severity of symptoms associated with upper respiratory tract infection by two-third and reduced the duration of the common cold episode approximately by half. In conclusion, SJP - 002 reduced the severity and duration of common cold episodes. These findings warrant further investigation of SJP - 002 in double-blind, placebo-controlled clinical trials.