Pharmazie最新文献

{"title":"Investigations on 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,2-<i>a</i>]pyridazin-1-amines and related compounds: synthesis, chemical behaviour, structure elucidation and iNOS inhibitory activity.","authors":"O Morgenstern, U Giesen, T Garn, M Freitag, K Schmidt, A Großmann, A Trettin, N Thämlitz, C Lemmerhirt","doi":"10.1691/ph.2024.4524","DOIUrl":"10.1691/ph.2024.4524","url":null,"abstract":"<p><p>The present work reports on the preparation of the hitherto unknown title compounds <b>5,</b> with various synthetic routes described. The initially pursued concept of S-N exchange with varioius 1-substituted 3-methylsulfanyl-5,6,7,8-tetrahydro-1 <i>H</i> -[1,2,4]triazolo[1,2- <i>a</i> ]pyridazines <b>4</b> by using nitrogen nucleophiles was only marginally successful. The reactions proceeded slowly and the yields were low, mainly because of the pronounced formation of 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,2- <i>a</i> ]pyridazin-1-imines <b>7</b> by oxidation of the heterocyclic amines <b>5</b> initially formed. The integration of the synthesis of 3-acylsulfanyl analogues with the more reactive leaving groups also failed. On the other hand, the cyclization of the hydrohalides of hexahydropyridazine-1-carboximidamide with aromatic aldehydes and some low molecular weight ketones gives significantly better results in the synthesis of the title compounds <b>5</b>. The use of the hydrochloride <b>6b</b> proved to be advantageous in comparison to the hydroiodide <b>6a</b> because the yields were significantly better and the imines <b>7</b> formed at the same time only to a small extent. In addition, the starting compound <b>6b</b> can be prepared in a single-step synthesis in very good yield from hexahydropyridazine hydrochloride <b>1</b> and cyanamide. The cyclization of <i>N'</i> -phenylhexahydropyridazine-1-carboximidamide hydrochloride <b>6c</b> with substituted benzaldehydes gives the 3-aryl-substituted 2-phenyl-2,3,5,6,7,8-hexahydro <i>-1H</i> -[1,2,4]triazolo[1,2- <i>a</i> ] pyridazin-1-imines <b>8</b>. In the context with the study of the reaction of hexahydropyridazine-1-carboximidamide hydroiodide <b>6a</b> with cyclohexanone, the hexahydropyridazine-1-carboxamide <b>9</b> was specifically synthesized. This can be reacted with aromatic aldehydes to give the 5,6,7,8-tetrahydro-1 <i>H</i> -[1,2,4]triazolo[1,2- <i>a</i> ]pyridazin-1-ones <b>10</b> in very good yields. The results of the biological testing of representatives of the synthesized 5,6,7,8-tetrahydro-[1,2,4] triazolo[1,2-a]pyridazine-1-amines <b>5</b> show, in comparison to the already examined thions <b>3</b> and 3-methylsulfanyl derivatives <b>4,</b> significantly less inducible nitric oxide synthase (iNOS) inhibitory activity.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of a mass spectrometric analytical method for the quality assessment of insulin and its analogs.","authors":"B A Pajaziti, M Andrási, D Nebija, N Kemlendi, B Pajaziti","doi":"10.1691/ph.2024.4013","DOIUrl":"10.1691/ph.2024.4013","url":null,"abstract":"<p><p>The principal aim of this study was to optimize analytical methodology based on mass spectrometry for the evaluation of the quality of recombinant human insulin and its analogs. In this study ESI-MS was used to assess the quality of human insulin, short acting insulin analogs, insulin lispro, insulin aspart and insulin glulisine and long acting analogs including insulin glargine, insulin degludec, and insulin detemir, in respective pharmaceutical formulations. In this study, with the aimed to optimize analytical conditions, different factors influencing the analytical performance such as pH, ionic strength, sample dilution, organic solvent addition were addressed. The study results demonstrated that MS is a suitable technique for the analysis of biotechnological compounds like insulin and its analogs. Although the obtained results provide an important information regarding this methodology, further studies are needed to validate this analytical approach and check for its suitability to be used in the regulatory environment.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis and evaluation of factors contributing to the occurrence of immune-related adverse events with immune checkpoint inhibitors.","authors":"T Nagase, O Shima, N Maruhana, Y Miyazawa, S Yoshino, J Sato, H Yamada, K Shinozaki, K Ikeda","doi":"10.1691/ph.2024.4548","DOIUrl":"10.1691/ph.2024.4548","url":null,"abstract":"<p><p>In recent years, there has been a growing trend in the use of immune checkpoint inhibitors (ICIs) for treating a larger patient population. However, it is important to note that immune-related adverse events (irAEs) frequently arise as a result. Therefore, precise patient monitoring becomes essential. We present the findings of a retrospective study conducted at the International University of Health and Welfare Narita Hospital (referred to as \"our hospital\") that aimed to identify risk factors linked to the occurrence of irAEs. The study focused on analyzing various factors, including therapeutic and lifestyle backgrounds, as well as laboratory values of patients who received ICI treatment and were subsequently diagnosed with irAE. The study included patients who met the eligibility criteria for ICIs (both single agent and combination therapy) as well as ICI in combination with anticancer drugs. The inclusion period for the study encompassed April 2020 to May 2022 at our hospital. The fifty patients were divided into two groups based on the severity of irAEs: the first group consisted of patients with irAE Grade 2 or lower (referred to as irAE Grade under 2), while the second group included patients with irAE Grade 3 or higher (referred to as irAE Grade over 3). Statistical analysis revealed significant differences in age (p=0.027) and CRP (C-reactive protein) levels (p=0.008) among the background factors when comparing the two groups. Additionally, statistically significant differences were observed among different ICI treatment groups in the occurrence of irAEs (p=0.035). however, it was indicated to be a relatively weak correlation. Moving forward, we shifted our focus to examine the frequency of irAEs in relation to exposure. However, we did not observe any significant correlation between exposure and irAE grade. Additionally, even when exposure was doubled through the use of ipilimumab in combination with ICIs (referred to as \"Mod exposure\"), no correlation was found. Exposure was further categorized into three groups: the PD-1 group, PD-L1 group, and PD-1 + CTLA-4 group. However, no significant correlation was observed between exposure in any of these groups and the grade of irAEs. Similarly, no significant correlation was observed between the dosage of ICI in the fixed-dose group and the weight-based dosage group with exposure and irAE Grade. Based on our study findings, there is a suggestive relationship between age and CRP levels and the occurrence of irAEs of Grade 3 or higher. These factors may play a role in contributing to the development of more severe irAEs.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occurrence of somnolence and respiratory depression induced by pregabalin and mirogabalin use and the influence of opioid treatment using the Japanese adverse drug event report database.","authors":"H Kato, T Koseki, M Kondo","doi":"10.1691/ph.2024.4528","DOIUrl":"10.1691/ph.2024.4528","url":null,"abstract":"<p><p><i>Background:</i> Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. <i>Methods:</i> Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically \"pregabalin\" and \"mirogabalin besilate.\" Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were \"Somnolence (10041349)\" and \"Respiratory depression (10038678).\" To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. <i>Results:</i> Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin (<i>p</i> = 0.004). <i>Conclusion:</i> While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.","authors":"H Nishiba, A Nagamine, H Yashima, Y Takahashi, Y Higuchi, N Sekizaki, H Nakamura, T Araki, N Takama, N Koitabashi, T Nakajima, Y Kaneko, Y Ohyama, T Yokoyama, K Imai, M Kurabayashi, K Yamamoto, K Obayashi","doi":"10.1691/ph.2024.4546","DOIUrl":"10.1691/ph.2024.4546","url":null,"abstract":"<p><p>Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in <i>VKORC1</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP4F2</i>, <i>GGCX</i>, and <i>APOE</i> in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [<i>VKORC1</i> rs9923231, <i>CYP2C9</i> rs1057910, <i>CYP4F2</i> rs2108622, <i>CYP2C19</i>^* <i>2</i> (rs4244285) and^* <i>3</i> (rs4986893), <i>GGCX</i> rs699664 and rs12714145, and <i>APOE</i> rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (^β = -0.445). <i>VKORC1</i> rs9923231 AA, <i>CYP4F2</i> rs2108622 CT/TT, <i>GGCX</i> rs12714145 CT/TT, and <i>CYP2C9</i> rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and β = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of <i>VKORC1</i> rs9923231, <i>CYP4F2</i> rs2108622, <i>GGCX</i> rs12714145, and <i>CYP2C9</i> rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism of baicalin by different microbiota determined by MimiCol.","authors":"D-S Seradj, L Neubauer, S Senekowitsch, W Weitschies, P Schick","doi":"10.1691/ph.2024.4014","DOIUrl":"10.1691/ph.2024.4014","url":null,"abstract":"<p><p>Substances metabolised by the intestinal microbiota can be used as colon markers and are gaining importance. The flavonoid glycoside baicalin has been described in the literature to be metabolised by the intestinal microbiota. The aim of this work was to investigate how the biotransformation of baicalin to baicalein is related to the intestinal microbiota. For this purpose, stool samples from healthy volunteers with different dietary habits were used. From the pre-cultured stool samples, different standard microbiota were obtained which were used for the subsequent metabolism studies in the <i>in vitro</i> model MimiCol. MimiCol represents the ascending section of the colon, the <i>colon ascendens</i>, in terms of available volume, pH-value, redox potential and bacterial abundance. While during the experiments with added standard microbiota a metabolism of baicalin to baicalein could be detected, this was not the case in a series of experiments without added microbiota. This confirmed the hypothesis that the metabolism of baicalin relies on the bacterial species that are present in the colon. The data collected in the MimiCol therefore support the use of baicalin as a potential marker for the determination of the colon arrival. This can be explained by the fact that baicalin in its native form is poorly absorbed from the gastrointestinal tract. Enzymes of the colonic microbiota, namely β-glucuronidases, hydrolyze baicalin to the aglycone baicalein. The resulting aglycone can be absorbed through the intestinal mucosa and detected in blood plasma. This potentially enables the use of baicalin as a marker to determine the time of arrival in the colon.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of apixaban anticoagulation in a patient requiring therapeutic plasma exchange: a case report and a literature review.","authors":"A Pilková, J M Hartinger, I Malíková, V Satrapová, D Šťastná, V Tesař, O Slanař","doi":"10.1691/ph.2024.4550","DOIUrl":"10.1691/ph.2024.4550","url":null,"abstract":"<p><p>Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.","authors":"T Hirose, K Mori, M Kimura, S Yamashita, H Hayashi, E Usami, T Tanase","doi":"10.1691/ph.2024.4510","DOIUrl":"10.1691/ph.2024.4510","url":null,"abstract":"<p><p>Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with changes in tacrolimus blood concentration after food initiation in patients with ulcerative colitis.","authors":"N Yoshikawa, T Nagatomo, Y Matsusaki, T Yokota, Y Yamada, R Ikeda","doi":"10.1691/ph.2024.4501","DOIUrl":"10.1691/ph.2024.4501","url":null,"abstract":"<p><p>The therapeutic effect of tacrolimus against ulcerative colitis (UC) is correlated with its trough blood concentration. Conventionally, oral tacrolimus for the treatment of UC is initiated under fasting conditions; once the symptoms improve, food intake is resumed. Tacrolimus blood concentration decreases with food intake compared with that under fasting conditions. The aim of this study was to explore the characteristics of patients with UC whose tacrolimus blood concentrations tended to decrease after food initiation. Medical data of 13 patients with UC and treated with tacrolimus were retrospectively obtained. The participant characteristics associated with the changes in tacrolimus blood concentrations after food initiation were analyzed using regression analysis based on the rate of decrease in the concentration/dose (C/D) ratio after food initiation. Single regression analysis showed that the number of days required from tacrolimus initiation to food resumption (<i>P</i> = 0.0071) and individual differences in the increase in tacrolimus blood concentration after administration (<i>P</i> = 0.0247) were significantly associated with the rate of decrease in the C/D ratio after food initiation. Furthermore, multiple regression analysis showed a significant effect of the number of days to food resumption (<i>P</i> = 0.0004) and individual differences in the increase in tacrolimus blood concentration after administration (<i>P</i> = 0.0012). The results suggest that the degree of change in blood tacrolimus concentration after food initiation may be related to the severity of the symptoms and pathology of UC. Early identification of participant characteristics may help control tacrolimus blood concentration fluctuations after food initiation.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-edematous effects of epinastine, cetirizine and its enantiomers in λ-carrageenan-induced edema in rat hind paw.","authors":"K Taguchi, V T G Chuang, M Ozawa, Y Sakamoto, R Hara, O Iketani, Y Enoki, J Kizu, S Hori, K Matsumoto","doi":"10.1691/ph.2024.4518","DOIUrl":"10.1691/ph.2024.4518","url":null,"abstract":"<p><p>Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H₁ -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H₁-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H₁-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H₁ -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H₁ -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.</p>","PeriodicalId":20145,"journal":{"name":"Pharmazie","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}