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The present work aims to present two new concepts concerned with chiral separation. First, chiral separation of some enantiomeric drugs, using micelle-based liquid chromatography without any chiral selector, whether in the stationary phase or the mobile phase, was performed. The surfactants used were anionic; sodium dodecyl sulphate, and cationic; cetrimide. The studied analytes include phenyl-ephrine hydrochloride (PHR), cetirizine dihydrochloride (CTZ), and mebeverine hydrochloride (MBV). Successful separation of the enantiomers was attained, giving promising results that may cause a revolution in chiral separation, predicting the possibility of simply prepared aqueous micellar mobile phases of carrying chiral selector ability. The second motive of this work is studying the compatibility of hybrid micelle liquid mobile phases with chiral columns separating CTZ, using cellulose 1 chiral column as a model example. This study may be an environmentally safe substitute for the normal phase mode of elution that is usually applied for chiral separation consuming large amounts of hazardous organic solvents. [ABSTRACT FROM AUTHOR]

Post-burn pruritis is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives including gabapentin in its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating post-burn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n=23), Gabapentin (n=23), or Cetirizine plus Gabapentin (n=23). Baseline assessment of the intensity or the severity of pruritus was evaluated after which treatment commenced with standard doses of the three study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7 and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine's 61.8%. The combined effect of cetirizine and gabapentin was comparable to using gabapentin alone. When itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7% whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of post-burn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, a low-dose gabapentin could be added if cetirizine is the drug intended for its treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Multiple human-induced environmental stressors significantly threaten global biodiversity and ecosystem functioning. Climate warming and chemical pollution are two widespread stressors whose impact on freshwaters is likely to increase. However, little is known about the combined effects of warming on the bioaccumulation of environmentally relevant mixtures of emerging contaminants, such as pharmaceutically active compounds (PhACs) in freshwater biota. This study investigated the bioaccumulation of a mixture of 15 selected PhACs at environmentally relevant concentrations in common freshwater macroinvertebrate taxa, exposed to ambient temperatures and warming (+4 °C) during the warm and cold seasons in two outdoor mesocosm experiments. Nine PhACs (carbamazepine, cetirizine, clarithromycin, clindamycin, fexofenadine, telmisartan, trimethoprim, valsartan and venlafaxine) were dissipated faster in the warm season experiment than in the cold season experiment, while lamotrigine showed the opposite trend. The most bioaccumulated PhACs in macroinvertebrates were tramadol, carbamazepine, telmisartan, venlafaxine, citalopram and cetirizine. The bioaccumulation was taxon, season and temperature dependent, but differences could not be fully explained by the different water stability of the PhACs and their partitioning between water and leaf litter. The highest water-based bioaccumulation factors were found in Asellus and Planorbarius. Moreover, the bioaccumulation of some PhACs increased with warming in Planorbarius, suggesting that it could be used as a sentinel taxon in environmental studies of the effects of climate warming on PhAC bioaccumulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Katerina Grabicova reports financial support was provided by Czech Science Foundation. Claire Duchet reports financial support was provided by Czech Science Foundation. Helena Svecova reports financial support was provided by Czech Science Foundation. Tomas Randak reports financial support was provided by Czech Science Foundation. David S. Boukal reports financial support was provided by Czech Science Foundation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Baddi-Barotiwala-Nalagarh (BBN) region of Indian Himalayas is one of the most important pharmaceutical industrial clusters in Asia. This study investigated the distribution, and ecological and human health risks of four most frequently used pharmaceuticals [ciprofloxacin (CIP), norfloxacin (NOR), cetirizine (CTZ) and citalopram oxalate (ECP)] when co-occurring with metal ions in the Sirsa river water of the BBN region. The concentration range of the selected pharmaceuticals was between 'not detected' to 50 μgL -1 with some exception for CIP (50-100 μgL -1 ) and CTZ (100-150 μgL -1 ) in locations directly receiving wastewater discharges. A significant correlation was found between the occurrences of NOR and Al (r 2  = 0.65; p = 0.01), and CTZ and K (r 2  = 0.50; p = 0.01) and Mg (r 2  = 0.50; p = 0.01). A high-level ecological risk [risk quotient (RQ) > 1] was observed for algae from all the pharmaceuticals. A medium-level risk (RQ = 0.01-0.1) was observed for Daphnia from CIP, NOR and ECP, and a high-level risk from CTZ. A low-level risk was observed for fishes from CIP and NOR, whereas CTZ and ECP posed a high-level risk to fishes. The overall risk to ecological receptors was in the order: CTZ > CIP > ECP > NOR. Samples from the river locations receiving water from municipal drains or situated near landfill and pharmaceutical factories exhibited RQ > 1 for all pharmaceuticals. The average hazard quotient (HQ) values for the compounds followed the order: CTZ (0.18) > ECP (0.15) > NOR (0.001) > CIP (0.0003) for children (0-6 years); ECP (0.49) > CTZ (0.29) > NOR (0.005) > CIP (0.001) for children (7-17 years), and ECP (0.34) > CTZ (0.21) > NOR (0.007) > CIP (0.001) for adults (>17 years). The calculated risk values did not readily confirm the status of water as safe or unsafe because the values of predicted no-effect concentration (PNEC) would depend on various other environmental factors such as quality of the toxicity data, and species sensitivity and distribution, which warrants further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) have been shown to be potentially closely related, but the relationship between these conditions, particularly the possibility of a causal link, is not fully understood. This study used Mendelian randomization (MR) to assess the causal relationship between these two disorders., Methods: We extracted genome-wide association study data sets for GERD and CRS from publicly available gene summaries, and used MR to conduct a causal inference analysis. The main robustness test used in this study included MR-Egger regression, a leave-one-out sensitivity test, and multivariate MR (MVMR)., Results: GERD increased the risk of developing CRS by 36%, based on the inverse-variance weighted method, a statistically significant association (odds ratio [OR] 1.360, 95% confidence interval [CI] 1.179-1.568, P < 0.001). Other MR assessment methods, such as weighted median, simple mode, and weighted mode, similarly observed a significant increase in the risk of CRS occurrence (OR 1.434, 95% CI 1.186-1.734, P < 0.001; OR 1.927, 95% CI 1.166-3.184, P = 0.013; and OR 1.910, 95% CI 1.222-2.983, P = 0.006, respectively). No significant bias was found in the heterogeneity or pleiotropy tests (P = 0.071 and P = 0.700, respectively). Even after excluding possible mediators using MVMR, GERD appeared to significantly increase the risk of developing CRS (OR 1.013, 95% CI 1.008-1.023, P = 0.002)., Conclusions: This study provides new, significant evidence that GERD is genetically associated with a higher incidence rate of CRS. However, further research is needed to elucidate the potential underlying biological mechanisms of this relationship., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Cetirizine is frequently administered at an increased dosage in clinical practice and recommended by several guidelines. Nonetheless, the pharmacokinetic (PK) profile and real-world safety data remain insufficient in the Chinese pediatric population. The objective of the current study is to develop a population pharmacokinetic (PPK) model for cetirizine in Chinese pediatric patients and to investigate the rationale behind its off-label usage. Methods: A prospective cohort study was conducted, enrolling children who had been diagnosed with allergic diseases and prescribed cetirizine. The outcomes were safety and pharmacokinetic (PK) parameters. Cetirizine concentrations were measured using a pre-established analytical method. Subsequently, a PK model was developed, followed by model evaluation and simulation. The developed PK model was employed to investigate the drug exposure differences across various age groups and to simulate scenarios of potential overdose. Results: Sixty-three children were enrolled, and 24 of them received a cetirizine dose exceeding the recommended dosage. A PPK model, based on published literature, served as the basis of our analysis, with adjustment made to estimate certain parameters. The final model evaluation and validation indicated accurate predictive performance and robust parameter estimation. Simulations conducted for the label-dose among age 1-12 indicated median maximum concentration at steady state (C max,ss ) of 7 year old children could be the highest. The model was also used to predict the off-label dose scenarios and overdose patient to support the clinical decision. There were no adverse drug reactions in either group. Conclusion: This study provides evidence-based and model-based exploration for optimizing cetirizine usage in Chinese pediatric patients. The cetirizine PPK model showed accurate predictive performance and could be utilized to simulate individual patient exposure in real-world clinical scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Tan, Yang, Yu, Yao, Zhou, Liu and Zhou.)

Abstract Paracetamol (PAR), Pseudoephedrine hydrochloride (PSE) and cetirizine dihydrochloride (CET) is a ternary mixture that composes tablets which are popular for the relief of flu in Egypt. The spectra of the drugs were overlapped and no spectrophotometric methods were reported to resolve the mixture. This research proposes four spectrophotometric methods that are efficient and require water only as a solvent. The first method was ratio subtraction-ratio difference method (RSDM) where PAR was initially removed from the mixture by ratio subtraction and determined at 292.4 nm, then PSE and CET were quantified by subtracting the amplitudes of their ratio spectra between 257.0 and 230.0 nm for PSE and between 228.0 and 257.0 nm for CET. The second method was derivative ratio spectra—zero crossing (DRZC) which was based on determining both PSE and CET from the zero-crossing points of the first and third derivative of their ratio spectra at 252.0 and 237.0 nm, respectively while PAR was determined using its first derivative at 292.4 nm. Moreover, the ternary mixture was resolved using successive derivative ratio (SDR) method where PAR, PSE and CET were determined at 310.2, 257.0 and 242.4 nm, respectively. The fourth proposed method was pure component contribution algorithm (PCCA) which was applied to quantify the drugs at their λmax. Recovery percentages for RSDM were 100.7 ± 1.890, 99.69 ± 0.8400 and 99.38 ± 1.550; DRZC were 101.8 ± 0.8600, 99.04 ± 1.200 and 98.95 ± 1.300; SDR were 101.9 ± 1.060, 99.59 ± 1.010 and 100.2 ± 0.6300; PCCA were 101.6 ± 1.240, 99.10 ± 0.5400 and 100.4 ± 1.800 for PAR, PSE and BRM; respectively. The suggested methods were effectively applied to analyze laboratory prepared mixtures and their combined dosage form.

Cetirizine, a piperazine-derivative second-generation antihistaminic, is used for a wide variety of disorders such as urticaria, eczema, and allergies. Adverse reactions due to this drug are usually rare, especially fixed drug eruption (FDE), a delayed cell-mediated hypersensitivity reaction, is scarce. Here, we report a case of cetirizine-induced FDE. A 34-year-old female developed hyperpigmented, itchy patches over both forearms, legs, feet, and right side of the chest after taking tablet cetirizine for dry cough with similar episode 2 years back on the same sites. The patient responded slowly with conservative treatment and the lesions disappeared after 10 days. She was advised to avoid the causative in near future. This case report highlighted FDE due to an antihistaminic which themselves will be prescribed to treat allergies.

Background: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis and includes tear film dysfunction. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs, lubricants and methods of administration, there is a need to update new treatments to optimize the care of ocular allergy patients. Methods: An overview of mediators, clinical characteristics and management is provided in a summary format. Results: Lubricants (best when refrigerated provide immediate relief that is short lived (several minutes) due to its dilutional effect on mediators and pollen in the tear film. Immediate and longer-term benefit occurs from different topical and oral medications - primarily histamine receptor agonists. Conclusion: The newest prescription topical ophthalmic histamine H1 receptor antagonist (an inverse agonist) to be approved by the U.S. Food and Drug Administration in the past 10 years (U.S. NDA approved May 30, 2017) is cetirizine ophthalmic solution for the treatment of ocular itching with allergic conjunctivitis in adults and in children more than 2 years old. [ABSTRACT FROM AUTHOR]

Levocetirizine is classified as a second‐generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate‐release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study. [ABSTRACT FROM AUTHOR]

Aim: This work aimed to develop topical nanoemulsion gels of cetirizine, a second-generation antihistamine, to avoid its oral intake drawbacks and enhance skin permeation. Methods: Cetirizine nanoemulsions were formulated and characterised for their particle size, polydispersity index, zeta potential, drug release and drug permeation through rat skin. The optimised formulation, obtained using 23 full factorial design, was incorporated in carbopol and chitosan gels and evaluated clinically for urticaria treatment. Results: The optimised formulation had particle size of 32.015 ± 1.87 nm, polydispersity index of 0.29 ± 0.04, zeta potential of –19.31 ± 0.43 mV, cetirizine percent released of 98.50 ± 1.23% and permeability coefficient of 7.65 cm.h−1. Cetirizine nanoemulsion gels were more effective than their control gels in urticaria treatment with significant decrease in the degree of wheals and itching and higher recovery percent. Conclusion: Cetirizine nanoemulsion topical gels are expected to be a rational and effective tool for avoiding cetirizine oral side effects and targeting the affected skin. [ABSTRACT FROM AUTHOR]

Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug‐drug interaction between GBP and cetirizine (CTZ), an inhibitor of transporters for organic cations. An open‐label, 2‐period, crossover, nonrandomized clinical trial was conducted in patients with neuropathic pain to evaluate the effect of CTZ on GBP pharmacokinetics. Twelve participants were treated with a single dose of 300 mg GBP (treatment A) or with 20 mg/d of CTZ for 5 days and 300 mg GBP on the last day of CTZ treatment (treatment B). Blood sampling and pain intensity evaluation were performed up to 36 hours after GBP administration. The interaction of GBP and CTZ with transporters for organic cations was studied in human embryonic kidney (HEK) cells expressing the organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and OCTN1. CTZ treatment resulted in reduced area under the concentration‐time curve and peak concentration compared with treatment A. In treatment B, the lower plasma concentrations of GBP resulted in reduced pain attenuation. GBP renal clearance was similar between treatments. GBP has low apparent affinity for OCT2 (concentration of an inhibitor where the response [or binding] is reduced by half [IC50] 237 µmol/L) and a high apparent affinity for hMATE1 (IC50 1.1 nmol/L), hMATE2‐K (IC50 39 nmol/L), and hOCTN1 (IC50 2.1 nmol/L) in HEK cells. At therapeutic concentrations, CTZ interacts with hMATE1 and OCTN1. In summary, CTZ reduced the systemic exposure to GBP and its effect on neuropathic pain attenuation. However, CTZ × GBP interaction is not mediated by the renal transporters. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of cetirizine on the fibrosis of skin tissue in systemic sclerosis (SSc) mice and its mechanism of action. Methods: Thirty-two BALB/C mice were randomly divided into a blank group, a model group, a cetirizine low-dose group, and a cetirizine high-dose group, with eight in each group. The blank group was injected with normal saline on the back, and the other three groups were injected with bleomycin on the back to prepare SSc mouse models. The mice were injected once a day for 28 consecutive days, while the normal group and the model group were given saline. The dose group was administrated intragastrically at 2 mg/kg and 5 mg/kg, respectively, for 28 consecutive days. Detect the thickness of the dermis by taking the skin tissue in the back injection area of each group. Hematoxylin-eosin staining (HE) and Masson staining. Sample hydrolysis method to detect hydroxyproline (HYP) content in skin tissue. Immunohistochemical detection of a-smooth muscle actin (a-SMA) expression in skin tissues. Enzyme-linked immunosorbent assay (ELISA) to detect serum interleukin (IL-6, IL-10) and transforming growth factor (TGF-a and TGF- ß1). Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of collagen type I (COL1A1), type III collagen (COL3A1), Smad homolog 3 (Smad3), and TGF- ß1 mRNA. Western blot was used to detect the expression levels of COL1A1, COL3A1 and p-Smad3. Results: Compared with the blank group, the dermis thickness and HYP content of the model group increased, the skin tissue lesions and fibrosis were more severe, the a-SMA positive expression intensity in the skin tissue was higher, and the serum IL-6, IL-10, TGF-a, TGF-ß1 content increased, COL1A1, COL3A1, Smad3, TGF-ß1 mRNA expression levels increased in skin tissues, COL1A1, COL3A1, p-Smad3 protein expression increased, the differences were statistically significant (P<0.05). Compared with the model group, the dermal thickness and HYP content of the low and high dose cetirizine groups were reduced, the degree of skin tissue lesions and fibrosis was improved, the expression of a-SMA in skin tissues was weakened, the levels of IL-6, IL-10, TGF-a, TGF-ß1 in serum were reduced, the expression levels of COL1A1, COL3A1, Smad3 and TGF-ß1 in skin tissues were reduced, and the expression levels of COL1A1, COL3A1, and p-Smad3 proteins were reduced, the decrease in the high-dose group was more significant, and the differences were statistically significant (P<0.05). Conclusion: Cetirizine can improve the degree of fibrosis of skin tissue in SSc mice and reduce the immune inflammation response. The mechanism of action is related to the TGF-ß1/Smad3 signaling pathway. [ABSTRACT FROM AUTHOR]

During manufacturing of tablet dosage forms, monitoring of processing parameters of machines/equipments play an important role in inherent qualities of manufactured tablets. If these processing parameters are not controlled as per defined specifications mentioned in batch manufacturing record of said batch, then it will impact its ideal characteristics/physical properties as well as its performance and effectiveness in biological system. Therefore it is very important to monitor processing parameter like speed of compression machine during compression stage of tablet manufacturing. In this study, an attempt has been made to demonstrate impact of variation of processing parameter (compression machine speed) on ideal properties like weight variation, hardness, disintegration time and friability of tablet dosage form manufactured by using active materials of Ibuprofen, Loperamide Hydrochloride and Cetirizine Dihydrochloride. In this study individual tablet dosage forms have been formulated by using mentioned active drugs along with similar excipients. Individual tablets samples were collected after subjecting compression machine to slow, optimum and fast compression speed for carrying out respective in-process tests of weight variation, hardness, disintegration time and friability test. Thereafter an comparative analysis have been made through this study to demonstrate impact of compressing machine speed on ideal characteristics of tablet dosage forms. [ABSTRACT FROM AUTHOR]

Cetirizine as general OTC anti-allergic drug was evaluated through paper chromatography. Twelve cetirizine compositions were analysed wherein each tablet and syrups were six in number. Seven solvent systems were experimented from which chloroform and methanol in ratio 50:50 proved to be best solvent system for both cetirizine tablet and syrup compositions. Other solvent system that showed clear separation of spots were n-hexane, toluene and diethyl ether in ratio 65:25:10 and acetone and methanol in ratio 90:10 for tablet and syrup preparations respectively. Iodine fuming technique and UV radiations were also utilized for visualising some unidentified and invisible spots during the examination procedures. [ABSTRACT FROM AUTHOR]

Salivary secretions are a common problem faced by the dental practitioner, mostly while taking impressions. Saliva hampers the flow of the impression material into the sulcus area, thereby preventing the recording of the area. Hence, certain drugs like antisialogogue can be used to aid in controlling the salivary flow. The aim of this study is to check the prevalence of two antisialogogues namely, Cetirizine and Propantilane bromide and their correlation with various parameters, such as age, gender and sextant. The subjects for this retrospective study were selected from June 2019 to May 2020. The antisialogogues to be tested were divided into two groups: Group 1: Cetirizine and Group 2: Propantheline Bromide. Frequencies of the antisialogogues used were checked and Chi-square test was used to check the correlation. It was observed that Cetirizine was more commonly used than Propantilane bromide. When the correlation with age was checked, it was observed that both the antisialogogues were common in younger patients. When the correlation with gender was checked, it was observed that both the antisialogogues were more common in males than females.When the correlation with age was checked, it was observed that Cetirizine was more common in sextant 2, whereas Propantheline bromide was more common in sextants 1, 2 and 6. Within the limitations of the study, it can be concluded that the preference of Cetirizine was more than propantheline bromide but more number of studies with a larger sample size needs to be done. [ABSTRACT FROM AUTHOR]

Immediate administration of intramuscular epinephrine to a patient experiencing anaphylaxis is the first-line therapy for this life-threatening allergic reaction. Alhough anaphylaxis is generally a rare occurrence, it has dire consequences if left untreated. In infants, anaphylaxis is typically triggered by exposure to egg, cow's milk, or peanuts. The rapid onset of symptoms in multiple organ systems makes an accurate diagnosis in infants difficult because there are numerous ways in which anaphylaxis may present. The symptoms of infant anaphylaxis are often underrecognized or misdiagnosed for less serious illnesses or even normal findings, including drooling, loose stools, and irritability. Because infants are mostly nonverbal--and most pediatric emergency department visits for anaphylaxis cases are the first diagnosis--ascertaining potential exposure to common allergens is difficult; this further complicates diagnosis in these youngest patients for whom the clinical presentation of anaphylaxis varies widely. A key factor in diagnosing anaphylaxis is the temporal profile of symptom development following allergen exposure; however, some children with anaphylaxis develop symptoms that reoccur hours or days after an initial anaphylactic reaction, making diagnosis challenging. Advanced practice nurses are often the first health care provider to encounter a patient who may be experiencing anaphylaxis. Although diagnostic criteria exist for anaphylaxis, specific criteria for the diagnosis of anaphylaxis in infants have not been developed. As such, it is important to understand and recognize the variable presentation of anaphylaxis in infants and to rapidly diagnose and treat with epinephrine. [ABSTRACT FROM AUTHOR]

Introduction: Cetirizine hydrochloride (CTZ) is a second-generation antagonist of H1 receptors. It is a non-sedating type antihistamine, orally active. It is used, mainly, in the symptomatic treatment of seasonal rhinitis and conjunctivitis as well as pruritus and urticaria of allergic origin. Objective: The objective of the study was to develop and validate a modified isocratic reversed-phase high-performance liquid chromatographic/ultraviolet (UV) analytical method to be more sensitive, accurate, and reproducible for quantification of CTZ in human plasma to be applied for studying the pharmacokinetics (PK) of CTZ after a single oral dose of Cetirizine® 10 mg tablet. Materials and Methods: Cetirizine was extracted from plasma samples by applying a liquid-liquid technique in dichloromethane. Samples were analyzed by Phenomenex C8 column (150 × 4.6 mm, 5 μm). A waters high-performance liquid chromatography (HPLC) system connected to a UV detector with autosampler were used to develop and validate the method. Diazepam was used as internal standard. A mixture of potassium dihydrogen phosphate (KH2PO4) buffer:methanol at a ratio of 50:50 (v/v) in isocratic mode was used as a mobile phase at a flow rate of 1.2 ml/min. The analysis was performed at ambient temperature and CTZ was monitored at a maximum wavelength (λmax) of 231 nm after injection a 55 μl sample into the HPLC system. The analytical method was validated according to standard guidelines. After that, the method was applied for PK study of CTZ tablets (Cetirizine®, Riyadh Pharma, Saudi Arabia). Cetirizine® 10 mg tablets were administered as a single dose to 12 healthy male adult volunteers (mean age of 28.5 ± 8.2 years) with fasting condition. Sixteen blood samples were withdrawn from each volunteer over 36 h period. From the plasma concentration-time data of each individual, the PK parameters; Cmax, tmax, AUC0-t, first-order terminal elimination rate constant (β), AUCt-∞, AUC0-∞, %AUCextra, Cmax/AUC0-∞, and t0.5 were calculated. Results: A specific peak area was observed for CTZ and diazepam at retention time (tR) of 12.4 and 15.9 min, respectively. Linearity was established at a concentration range of 10-500 ng/ml with the regression coefficient (R²) = 0.999. The lower limit of quantitation was identifiable and reproducible at 10 ng/ml with precision (as coefficients of variation [CV%]) of 4.45%. The CV% of the intraday and interday precision at 30, 250, and 400 ng/ml levels were found to be 3.616%, 1.006%, and 2.326%; and 6.798%, 1.869%, and 2.155%, respectively, which, were lower than the accepted criteria limits (15%). Accuracy for CTZ ranged from 93.545% to 102.458% at low, mid, and high concentration levels. The relative recovery (%) of CTZ at 30, 250, and 400 ng/ml was found to be 97.724%, 102.327%, and 101.586%, respectively. Stability at different conditions and in autosampler was also confirmed. The mean PK parameters of CTZ; Cmax, tmax, AUC0-t, β, AUCt-∞, AUC0-∞, AUCextra%, Cmax/AUC0-∞, and t0.5 were found to be; 271.971 ng/ml, 1.085 h, 2504.961 ng. h/ml, 0.083/h, 142.739 ng. h/ml, 2647.7 ng. h/ml, 5.537%, 0.104/h, and 8.396 h, respectively. Conclusions: The modified method was proved to be specific, sensitive, accurate, and precise for quantification of CTZ in human plasma. It can be confidently applied for PK then after, for bioavailability and bioequivalence studies. [ABSTRACT FROM AUTHOR]

Introduction: Chronic autoimmune urticaria (CAU) lasts over 6 weeks and is characterized by circulating IgE autoantibodies or IgG against IgE or IgE receptor. Aim: To assess the clinical, laboratory and histological effects of 4-week levocetirizine and montelukast therapy in patients suffering from CAU. Material and methods: Of 296 tested patients with chronic urticaria 40 had a positive ASST test. Only 17 (16 female/1 male; medium age: 44 years) fulfilled all study inclusion/exclusion criteria. The study was designed as an open, randomized trial with two arms: levocetirizine or montelukast treatment for 4 weeks following a 2-week wash-out period. All participants completed urticaria activity score (UAS) and visual analogue scale (VAS) questionnaires before and after both therapies. Blood samples and skin bioptats were obtained before and after treatment to evaluate COX-1 and COX-2 serum concentrations and skin expression. Results: Clinical response to therapy measured with the UAS and VAS was better in the levocetirizine group. Both drugs caused a significant decrease in COX-1 and COX-2 serum level. COX-1 and COX-2 expression in epidermal and dermal inflammatory infiltration did not change significantly in either study group, but a significant decrease of COX-1 expression was observed when the groups were combined for analysis, and the decrease in COX-2 expression in the epidermis was of borderline significance. Conclusions: The effectiveness of levocetirizine and montelukast in treating CAU may be partly related to the reduction of COX-1 and COX-2 serum level and tissue expression, but further studies on a larger group of patients are needed to support this observation. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that the Qingre Qushi (QRQS) formula can treat atopic dermatitis (AD), and its possible mechanism is related to the regulation of the IL-33/ST2 signaling pathway. However, the molecular mechanism of AD is complex, and various AD subtypes respond better to therapies aimed at distinct targets. This study aimed to investigate the multi-target mechanism of QRQS using experimental and network pharmacology studies. Flaky tail (FT) mice were treated with different concentrations of QRQS and cetirizine. The dermatitis score, scratching frequency, and histological evaluation were normatively evaluated. The levels of IgE and IgG1 in serum were tested using ELISAs. Using ELISA and RT-PCR, the expression of associated cytokines was determined. IL-17A-stimulated HaCaT cells were treated with QRQS to assess mRNA and protein expression. To elucidate the mechanism, a network pharmacology analysis based on active components derived from UPLC was conducted. Through molecular docking, we evaluated the binding affinity between the active constituents of QRQS and potential targets. Using UPLC, 177 active ingredients in QRQS were identified. Network pharmacology analysis showed that the anti-AD effect of the active ingredients was related to the IL-17 signaling pathway and its related targets. FT mice are characterized by Th17-dominated immune disorders. QRQS ameliorated AD-like symptoms and decreased dermatitis scores and scratching frequencies. After QRQS treatment, IL-17A expression was inhibited and IL-17 pathway-associated cytokines were downregulated. Along with changes in Th17-differentiation, QRQS suppressed the expression of IL-4, IL-13, and TNF-α. QRQS also decreased the expression of IL-6, IL-8, and COX-2 in HaCaT cells exposed to IL-17A. The anti-AD active doses are 3.86 g/kg/day in vivo and 100 μg/mL in vitro. QRQS has a multi-target immunoregulatory effect on AD and can improve the Th17-dominated inflammatory response by regulating the IL-17A signaling pathway. Quercetin, genistein, luteolin, and kaempferol are potential active ingredients. [Display omitted] [ABSTRACT FROM AUTHOR]

The goal of the present study was to develop a generic workflow to evaluate the chromatographic resolution in a design space and find replacement column for the new method. To attain this objective, a limited number of initial experiments have been performed, and a modeling tool was employed to study and compare design spaces obtained with different columns. By overlaying the different individual resolution maps (design spaces), it is possible to quickly identify a robust zone where the different columns meet a given resolution criterion. This new feature of the modeling tool is very useful for finding alternative columns for a given separation, rather than the usual column tests. It was also demonstrated that two different columns can be used as equivalents (replacement columns), providing sufficient resolution at the same working point and with a high degree of robustness. [Display omitted] • a new UHPLC method was developed for cetirizine impurity profiling to update the Ph. Eur. method. • a generic workflow has been proposed to suggest replacement columns for a given separation. • column comparison was based on the visualization and overlay of design spaces. • the new method was validated in accordance with international guidelines. [ABSTRACT FROM AUTHOR]

This study was done to determine the suppression index of Cetirizine to the skin prick test results to obtain a correction constant or factor that can be used to assess the results of the skin prick test in patients who cannot stop the use of antihistamines (Cetirizine). This pre and post test study design clinical trial involved 22 atopic allergy patients who seek medical treatment at the Allergy and Immunology Outpatient Clinic Dr. Soetomo Hospital. Skin prick tests were done twice (SPT1 and SPT2) using house dust mite allergen extract to all study subjecs. The first (SPT1) were done after washout of all antihistamine for 1 week prior the test. All study subjects were then given Cetirizine 10 mg once daily for 5 days and on day 6 we performed the second test (SPT2). Cetirizine suppresion index and correction factor were calculated by comparing the wheal area of SPT1 and SPT2. All 22 study subjects (6 males and 16 females) were sensitized to house dust mite allergen. Mean serum total IgE levels were 176.42 + 352.5 IU/dL. Mean wheal area generated by the positive control (histamine 1 mg/mL) in SPT1 was 7.53 + 7.31 mm2, and in SPT2 was 1.08 + 1.46 mm2. Mean wheal area generated by house dust mite allergen in SPT1 was 43.57 + 36 mm2, and in SPT2 was 10.28 + 8.47 mm2. Cetirizine suppression index for positive controls (histamine 10 mg/mL) was 94.63 + 7.90% (p=0.000), while the Cetirizine suppression index for house dust mite allergen is 72.31 + 13.96% (p=0.000). There was no significant influence of serum total IgE levels to Cetirizine suppression index (p=0.381). The correction constant based on the calculation was 1.9. In conclusion, Cetirizine suppression index to the mean wheals area generated by house dust mite allergen was 72.31% and the correction constant was 1.9. In allergic patients who cannot stop their antihistamine drugs, Cetirizine 10 mg once daily can be used as a replacement and they still be able to undergo skin prick tests. The actual wheal diameter (or area) of the skin prick test results can be calculated by multiplying the measured wheal diameter (or area) under the Cetirizine administration with the correction constant.

Goal of the study. To compare the efficacy of antihistamine drugs for the therapy of chronic urticaria taking into consideration their effect on the patients’ cognitive functions. Materials and methods. The study involved 178 patients with chronic urticaria who were divided into six groups taking second generation antihistamine drugs: Cetirizine (n = 38), Levocetirizine (n = 27), Fexofenadine (n=26), Ebastine (n = 33), Loratadine (n = 26) and Desloratadine (n = 28). The patients recorded dynamic changes in clinical symptoms of the disease (number of urticarial components, skin itching intensity, availability or absence of urticarial derniographism, angioedema signs and signs of the shortness of breath and reduced blood pressure) in their individual diaries. Baseline signs of the patients’ cognitive condition and those recorded during the treatment were studied using the Kraepelin’s arithmetic test (modified by Schulte), I.M. Lushchikhina’s verbal and visual thinking assessment method and method for memorizing ten words. The control group comprised 31 subjects without chronic urticaria. Results of the study. Ebastine and Fexofenadine are the most efficient antihistamine drugs for the treatment of chronic urticaria. At the same time, they do not have any negative effect on the patients’ cognitive functions so they can be recommended for long-term treatment of chronic urticaria. In spite of its evident positive therapeutic effect, Cetirizine reduces mental alertness and deteriorates thinking in patients with chronic urticaria. Because of this, the drug must be prescribed with care for long-term administration to those patients whose professional activities demand increased attention concentration. Loratadine has a positive effect on the patients’ attention and thinking. However, taking into consideration its low efficacy, the drug can be prescribed as the basis therapy for the treatment of light forms of chronic urticaria.