Ecological and human health risk assessment of pharmaceutical compounds in the Sirsa River of Indian Himalayas.

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 (r2 = 0.65; p = 0.01), and CTZ and K (r2 = 0.50; p = 0.01) and Mg (r2 = 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.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

The effect of warming and seasonality on bioaccumulation of selected pharmaceuticals in freshwater invertebrates.

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.

Causal analysis between gastroesophageal reflux disease and chronic rhinosinusitis.

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.

Transfer of cetirizine/levocetirizine into human breast milk and estimation of drug exposure to infants through breastfeeding: A human lactation study from the ConcePTION project.

Data on drug transfer into human breast milk are sparse. This study aimed to quantify concentrations of cetirizine and levocetirizine in breast milk and to estimate drug exposure to infants. Breastfeeding women at least 8 weeks postpartum and using cetirizine or its pure (R)-enantiomer levocetirizine were eligible to participate. Breast milk samples were collected at six predefined times during a dose interval (0, 2, 4, 8, 12 and 24 h after drug intake) at steady state. Infant drug exposure was estimated by calculating the absolute infant dose (AID) and the weight-adjusted relative infant dose (RID). In total, 32 women were eligible for final inclusion, 31 women using cetirizine and one woman using levocetirizine. Means of the individual maximum and average cetirizine milk concentrations were 41.0 and 16.8 µg/L, respectively. Maximum concentrations occurred on average 2.4 h after intake, and the mean half-life in milk was 7.0 h. Estimated AID and RID for cetirizine in a day were 2.5 µg/kg and 1.9%, respectively. The corresponding values for levocetirizine were 1.1 µg/kg and 1.9%. No severe adverse events were reported. Our findings demonstrate that the transfer of cetirizine and levocetirizine into breast milk is low and compatible with breastfeeding.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

[Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19].

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. AIM: The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. MATERIALS AND METHODS: The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. RESULTS: The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. CONCLUSION: In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

Continuous synthesis of BaFe2O4 and BaFe12O19 nanoparticles in a droplet microreactor for efficient detection of antihistamine drugs in oral fluid using surface-assisted laser desorption/ionization mass spectrometry.

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has received considerable attention as a complementary approach to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), offering substantial potential for analyzing molecules in the low-mass region. Herein, we propose a facile method, a microreactor for the synthesis of two types of barium ferrite (BaFe2O4 and BaFe12O19) nanoparticles (NPs) within moving droplets for detecting antihistamine (AH) drugs in oral fluid (OF). The synthesized BaFe2O4 and BaFe12O19 NPs exhibited small particle size, good ultraviolet absorption, and excellent performance in SALDI-MS, as determined by survival yield measurements. The limits-of-detection for AH drugs were in the range of 1 pg mL-1 to 100 ng mL-1, and spot-spot reproducibility of the SALDI substrates was satisfactory. Moreover, when analyzing cetirizine in OF, the obtained recoveries of cetirizine were 101% and 99% using BaFe2O4 and BaFe12O19 NP, respectively. Furthermore, the proposed method was validated by analyzing OF samples from a healthy volunteer who consumed a 5 mg levocetirizine tablet for seven days. SALDI-MS analysis confirmed the successful detection of endogenous components, the parent ion of cetirizine, and other exogenous substances. This study reports an advanced application of droplet microreactor technology for designing and synthesizing a wide range of novel and efficient SALDI-MS substrates for various applications.

Levocetirizine-Loaded Electrospun Fibers from Water-Soluble Polymers: Encapsulation and Drug Release.

Electrospun fibers containing levocetirizine, a BCS III drug, were prepared from three water-soluble polymers, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). Fiber-spinning technology was optimized for each polymer separately. The polymers contained 10 wt% of the active component. An amorphous drug was homogeneously distributed within the fibers. The solubility of the drug in the polymers used was limited, with a maximum of 2.0 wt%, but it was very large in most of the solvents used for fiber spinning and in the dissolution media. The thickness of the fibers was uniform and the presence of the drug basically did not influence it at all. The fiber diameters were in the same range, although somewhat thinner fibers could be prepared from PVA than from the other two polymers. The results showed that the drug was amorphous in the fibers. Most of the drug was located within the fibers, probably as a separate phase; the encapsulation efficiency proved to be 80-90%. The kinetics of the drug release were evaluated quantitatively by the Noyes-Whitney model. The released drug was approximately the same for all the polymers under all conditions (pH), and it changed somewhere between 80 and 100%. The release rate depended both on the type of polymer and pH and varied between 0.1 and 0.9 min-1. Consequently, the selection of the carrier polymer allowed for the adjustment of the release rate according to the requirements, thus justifying the use of electrospun fibers as carrier materials for levocetirizine.

Prioritization of pharmaceuticals and personal care products in the surface waters of Korea: Application of an optimized risk-based methods.

The occurrence of PPCPs in aquatic environments and their potential adverse effects on aquatic organisms have raised worldwide concerns. To address this issue, a study was conducted to analyze 137 selected PPCPs in Korean surface waters, and an optimized risk-based prioritization was performed. The results revealed that 120 PPCPs were detected, with 98 quantified at concentrations ranging from few ng/L to 42,733 ng/L for metformin. The 95% upper confidence limit (UCL95) of the mean value of the measured environmental concentration (MEC) for Metformin was about eight times higher than the second highest compound, dimethyl phthalate, indicating that antidiabetic groups had the highest concentration among the therapeutic groups. An optimized risk-based prioritization was then assessed based on the multiplication of two indicators, the Frequency of Exceedance and the Extent of Exceedance of Predicted No-Effect Concentrations (PNECs), which can be calculated using the traditional risk quotient (RQ) approach. The study found that clotrimazole had the highest risk quotient value of 17.4, indicating a high risk to aquatic organisms, with seven and 13 compounds showing RQ values above 1 and 0.1, respectively. After considering the frequency of exceedance, clotrimazole still had the highest novel risk quotient (RQf) value of 17.4, with 99.6% of its MECs exceeding PNECs. However, the number of compounds with RQf values above 1 decreased from seven to five, with cetirizine and flubendazole being excluded. Furthermore, only 10 compounds exhibited RQf values above 0.1. The study also observed significant differences in the results between risk-based and exposure-based prioritization methods, with only five compounds, cetirizine, olmesartan, climbazole, sulfapyridine, and imidacloprid, identified in both methods. This finding highlights the importance of considering multiple methods for prioritizing chemicals, as different approaches may yield different results.

The Elusive Structure of Levocetirizine Dihydrochloride Determined by Electron Diffraction.

Levocetirizine is an orally administrated, second-generation antihistaminic active pharmaceutical ingredient that has been used to treat symptoms of allergy and long-term hives for over 25 years. Despite the wide use of this compound, its crystal structure has remained unknown. Here we report the application of 3D electron diffraction (3D ED)/Micro-crystal electron diffraction (MicroED) to determine the crystal structure of Levocetirizine dihydrochloride directly from crystalline powders that were extracted from commercially available tablets containing the compound. We also showcase the utility of dynamical refinement to unambiguously assign absolute configuration. The results highlight the immense potential of 3D ED/MicroED for structure elucidation of components of microcrystalline mixtures that obviates the need to grow large-size single crystals and the use of complementary analytical techniques, which could be important for identification as well as for primary structural characterization.

Comparative study on the efficacy and safety of bepotastine besilate versus levocetirizine in chronic spontaneous urticaria: A randomised, open-label, parallel study.

Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.

Construction of a Zinc Oxide Nanorod-Modified Coated Wire Electrode for Potentiometric Determination of Levocetirizine Dihydrochloride in Its Pure and Combined Form.

BACKGROUND: Coated wire electrodes (CWEs) are considered the most effective and selective type of ion- selective electrodes because of the electroactive materials which are used in surface modification. OBJECTIVE: This study aims to construct the first potentiometric method for analysis of levocetirizine (LVZ) in its combination form with montelukast (MON) drug. METHODS: A novel potentiometric sensor which consists of a silver wire coated with zinc oxide (ZnO) nanorod modified with a polymeric membrane (combining ß-cyclodextrin and tetraphenyl borate, and plasticized with di-butyl phthalate) was constructed for the determination of LVZ·2HCl in its pure form and its combination dosage form. RESULTS: The fabricated sensor exhibited a linearity range of 5 × 10-6-1 × 10-2 mol/L with a Nernstian slope 57.88 mV/decade over the pH range 2-4.5. The effect of temperature on the constructed sensor was studied and it was found that the electrode worked effectively over 10-50°C. The electrode showed a fast response time and the lifetime of the electrode was found to be 72 days without significant change in the Nernstian slope value. The selectivity of the electrode toward LVZ was estimated in the presence of some obstructive ions. CONCLUSION: The method was validated according to International Council for Harmonisation of Technical Requirments for Registration of Pharmaceuticals for Human Use (ICH) rules and applied to the determination of LVZ in its pure and combined pharmaceutical dosage forms. HIGHLIGHTS: This article introduces the synthesis of the first coated wire electrode modified with zinc oxide (ZnO) nanorods for the determination of the drug levocetirizine. The results demonstrate the ability of electrochemical methods to analyze drugs in combination. The presented method excels over the other analytical methods in terms of sensitivity, selectivity, and simplicity.

Bioequivalence of Levocetirizine Hydrochloride Granules (Kangzhitai) in Healthy Subjects.

Objective: Levocetirizine hydrochloride is the R-enantiomer of cetirizine, which is a new-generation histamine H1 receptor antagonist with high safety, selectivity, and affinity. As a high-efficiency non-sedating antihistamine, levocetirizine hydrochloride has been widely used in the clinical treatment of skin, respiratory, and eye allergies. However, the bioavailability of levocetirizine hydrochloride granules remains to be determined. The study examined the relative bioavailability of the test drug (levocetirizine hydrochloride granules (Kangzhitai®)) and determined whether Kangzhitai® was bioequivalent to the reference drug (levocetirizine (Xyzal®)) in healthy individuals. Methods: Twenty eligible healthy male subjects were randomly divided into two groups. Group one received 5 mg of Kangzhitai®, followed by a 10-day wash-out period and 5 mg of Xyzal® on day 11. Group two received the same doses but in a reverse sequence. The subjects fasted for 12 h, and blood samples were collected before (blank) and after administration. The plasma concentration of Kangzhitai® was determined by HPLC-MS-MS. Pharmacokinetic parameters were analyzed using DAS 2.0 software. Results: The main pharmacokinetic parameters Cmax, Tmax, T1/2, AUC0-48, and AUC0-∞ of the Xyzal® and Kangzhitai® groups were as follows: (218.4 ± 46.4) µg/L vs. (213.6 ± 39.3) µg/L, (0.73 ± 0.32)/h vs. (0.75±0.3)/h, (9.2 ± 2.0) h vs. (8.9 ± 2.7) h, (1594.0 ± 337.2) µg·h/L vs. (1652.6 ± 383.5) µg·h/L, and (1683.2 ± 338.5) µg·h/L vs. (1753.7 ± 445.4) µg·h/L. The two-one-sided t tests of Cmax, AUC0-48, and AUC0-∞ showed that th and t1 were both higher than one-sided t0.05. The 90% confidence intervals (CI) for AUC0-48 and AUC0-∞ of Kangzhitai® did not exceed 80%-125% of AUC0-48 and AUC0-∞ of Xyzal®. The 90% CI for the Cmax of Kangzhitai® did not exceed 70%-143% of the Cmax of Xyzal®. There was no significant difference in Tmax between the two drugs. The relative bioavailability (F, assessed by AUC0-48) of Kangzhitai® vs. Xyzal® was 104.4±18.5%. No adverse events occurred during the drug administration. Conclusion: The results indicated that there was no significant difference in absorption between Kangzhitai® and Xyzal®, which confirmed the bioequivalence of the two drugs.

Separation and identification of cetirizine enantiomers in human urine by capillary electrophoresis and circular dichroism independent of their standards.

Enantioseparation and determination of chiral drugs are of vital importance in biochemical and pharmaceutical research due to the different biological activity, mechanism, and toxicity of individual enantiomers. As a second-generation H(1)-antagonist, cetirizine's pharmaceutical activity is mainly derived from the levocetirizine while the dextro-enantiomer is ineffective and even associated with side effects. Herein, the enantiomers of cetirizine were separated by capillary electrophoresis and identified by electronic circular dichroism. Satisfactory linear relationship was found between the circular dichroism signal at λmax and the electrophoretic peak area difference in the nonracemic mixture of enantiomers. It made possible identification and quantification of cetirizine enantiomers independent of single enantiomer standards. The method's feasibility was demonstrated on the enantiomeric excess experiments of oral drugs measured in human blank urine. Additionally, the separation and determination of cetirizine in human urine after administration were also realized by capillary electrophoresis, indicating the method was sensitive enough for pharmacokinetic study.

Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.

Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.

Comparison between topical cetirizine with minoxidil versus topical placebo with minoxidil in female androgenetic alopecia: a randomized, double-blind, placebo-controlled study.

Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).

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

Levocetirizine, a histamine H1-receptor antagonist, is prescribed to treat uncomplicated skin rashes associated with chronic idiopathic urticaria as well as the symptoms of both seasonal and continual allergic rhinitis. In this monograph, the practicality of using Biopharmaceutics Classification System (BCS) based methodologies as a substitute for pharmacokinetic studies in human volunteers to appraise the bioequivalence of immediate-release (IR) oral, solid dosage forms containing levocetirizine dihydrochloride was investigated, using data from the literature and in-house testing. Levocetirizine's solubility and permeability properties, as well as its dissolution from commercial products, its therapeutic uses, therapeutic index, pharmacokinetics and pharmacodynamic traits, were reviewed in accordance with the BCS, along with any reports in the literature about failure to meet bioequivalence (BE) requirements, bioavailability issues, drug-excipient interactions as well as other relevant information. The data presented in this monograph unequivocally point to classification of levocetirizine in BCS Class 1. For products that are somewhat supra-equivalent or somewhat sub-equivalent, clinical risks are expected to be insignificant in light of levocetirizine's wide therapeutic index and unlikelihood of severe adverse effects. After careful consideration of all the information available, it was concluded that the BCS-based biowaiver can be implemented for products which contain levocetirizine dihydrochloride, provided (a) the test product comprises excipients that are typically found in IR oral, solid drug products that have been approved by a country belonging to or associated with ICH and are used in quantities that are typical for such products, (b) data supporting the BCS-based biowaiver are gathered using ICH-recommended methods, and (c) all in vitro dissolution requirements specified in the ICH guidance are met by both the test and comparator products (in this case, the comparator is the innovator product).