• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.113-121
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• 1998

To clarify whether nizatidine, a $H_2$ receptor antagonist, has the cholinergic activity, the effects of nizatidine on the guinea pig ileum and on the acetylcholinesterase in human serum were studied. And, the mechanism of excitatory effect of nizatidine on the cholinergic system in ileum was also studied. Nizatidine caused a concentration-dependent contractile response by the guinea pig ileum. The $EC_{50}\;was\;53\;{\mu}M$ and the maximum response was at $300\;{\mu}M$. Ranitidine also caused a contractile response by the guinea pig ileum, but cimetidine and famotidine did not. The pretreatment with $H_1$ receptor antagonist did not affect the actions of nizatidine on the guinea pig ileum, but the pretreatment with atropine completely blocked them. Nizatidine significantly enhanced the acetylcholine-induced response of the guinea pig ileum, but not the pilocarpine-induced response. Nizatidine did not affect the histamine-induced response of the guinea pig ileum. Nizatidine still exerted the small excitatory effect on the guinea pig ileum pretreated with the high concentration of physostigmine. Nizatidine significantly inhibited the acetylcholinesterase in human serum. These results suggest that nizatidine exerts an excitatory effect on guinea pig ileum which seems to be associated with the cholinergic system, probably through an indirect mechanism, inhibition of acetylcholinesterase and/or increased release of acetylcholine.

• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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• pp.22-32
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• 1997

The gastrointestinal disorders (GI disorders) is one of the most common diseases in Korea. The community pharmacists are often faced with the complaints of symptoms due to the GI disorders. However the drugs used to treat the GI disorders are frequently abused by the patients themselves because these drugs are easily available and have high placebo effects. Therefore, we have reviewed the digestive diseases statistics of 1996 to find out the frequencies of the GI disorders in the outpatients of Samsung Medical Center. Using these statistic data, we figured out the frequently diagnosed GI disorders and analysed commonly used prescriptions from February 1st to 28th of 1997. In addition, we also evaluated the commonly used drugs in these prescriptions. About twenty thousands of patients visited the hopital because of their GI symptoms in 1996. It was found that dyspepsia, viral hepatitis, and gastric and duodenal ulcer disease are frequently diagnosed in these patients. In a point of view on other GI disorders, gastritis and duodenitis, irritable bowel syndrome, gastroesophageal reflux disease, constipation and diarrhea were commonly detected. And a number of drugs were prescribed to treat the GI disorders, which included the prokinetics, Histamine-2 receptor antagonists, proton pump inhibitor, antacids, tranquillizers, antidepressants, antispasmodics, laxatives and so on. Interestingly, there were many prescriptions composing of the antibiotic regimens to eradicate H. pylori which has been proven to cause peptic ulcers.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.282-290
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• 2019

Background: Ginsenoside Rg3 (G-Rg3) is the major bioactive ingredient of Panax ginseng and has many pharmacological effects, including antiadipogenic, antiviral, and anticancer effects. However, the effect of G-Rg3 on mast cell-mediated allergic inflammation has not been investigated. Method: The antiallergic effects of G-Rg3 on allergic inflammation were evaluated using the human and rat mast cell lines HMC-1 and RBL-2H3. Antiallergic effects of G-Rg3 were detected by measuring cyclic adenosine monophosphate (cAMP), detecting calcium influx, and using real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and in vivo experiments. Results: G-Rg3 decreased histamine release from activated mast cells by enhancing cAMP levels and calcium influx. Proinflammatory cytokine production was suppressed by G-Rg3 treatment via regulation of the mitogen-activated protein kinases/nuclear factor-kappa B and receptor-interacting protein kinase 2 (RIP2)/caspase-1 signaling pathway in mast cells. Moreover, G-Rg3 protected mice against the IgE-mediated passive cutaneous anaphylaxis reaction and compound 48/80-induced anaphylactic shock. Conclusion: G-Rg3 may serve as an alternative therapeutic agent for improving allergic inflammatory disorders.

• Clinical and Experimental Pediatrics
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• v.56 no.2
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• pp.68-74
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• 2013

Purpose: To evaluate the effectiveness of new management policies on the incidence of invasive Candida infections Methods: This observational study involved a retrospective analysis of the patients' medical records. In total, 99 very low birth weight infants, who were admitted to the neonatal intensive care unit at Ajou University Hospital from January 2010 to December 2011, were enrolled for the study. Period I, defined as the period before the revision of management policies, comprised 57 infants; whereas, period II, defined as the period after the implementation of new management policies, comprised 42 infants. The new management policies entailed a reduction in antibiotic and histamine type 2 receptor blocker (H2 blocker) use, duration of central venous catheterization, and duration of endotracheal intubation. Results: There was a significant overall decrease in the use of antibiotics including 3rd generation cephalosporin and H2 blockers (P<0.05), and a significantly lower incidence of invasive Candida infections in period II as compared to period I (0/42 vs. 6/57, respectively; P=0.037). Comparison between infants with invasive Candida infections (n=6) and those without (n=93) showed that gestational age (odds ratio [OR], 0.909; 95% confidence interval [CI], 0.829 to 0.996; P=0.042) and the duration of 3rd generation cephalosporin use (OR, 1.093; 95% CI, 1.009 to 1.183; P=0.029) were statistically significant risk factors. Conclusion: The new management policies effectively decreased overall use of antibiotics, especially 3rd generation cephalosporin, and H2 blockers, which led to a significantly lower incidence of invasive Candida infections.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.585-592
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• 2022

Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.57-62
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• 2001

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine $H_1-receptor$ antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, $Azeptin^{TM}$ (Bu Kwang Pharmaceutical Co., Ltd.) and $Azela^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $22.44{\pm}2.01$ years in age and $61.99{\pm}6.18\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 1 mg of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -6.45%, -2.60% and -7.14%, respectively, when calculated against the $Azeptin^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 96.65% and 88.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.40% and 17.65% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-14.87{\sim}1.97$ and $-12.92{\sim}7.72$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Azela^{TM]$ tablet is bioequivalent to $Azeptin^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.53-58
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 180 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Hanmi Fexofenadine Hydrochloride $Tablet^{\circledR}$ made by Hanmi Pharm. Co. and the reference product was Allegra $Tablet^{\circledR}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2\;{\time}\;2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were $log\;0.822{\sim}log \;1.142$ and $log\;0.848{\sim}log\;1.172$, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet is bioequivalent to Allegra Tablet.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.34-39
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 120 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration(KFDA). The test product was Hanmi Fexofenadine Hydrochloride Tablet $120mg^{(R)}$ made by Hanmi Pharm. Co. and the reference product was Allegra Tablet $120mg^{(R)}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2{\times}2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t\;and\;C_{max}$ were log $0.844{\sim}log$ 1.149 and log $0.833{\sim}log$ 1.109, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet 120 mg is bioequivalent to Allegra Tablet 120 mg.

• Korean Journal of Bronchoesophagology
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• v.9 no.1
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• pp.67-74
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• 2003

Larygopharyngeal reflux(LPR) is one form of the Gastroesophageal Reflux Diseases(GERD). It is known to cause various kinds of otolaryngologic symptoms such as hoarseness, globus sensation in throat, chronic throat clearing, and chronic cough, Disease entities diagnosed by otolaryngologists as posterior laryngitis, globus pharyngeus and reflux laryngitis should be suspected as LPR-related diseases. The nizatidine(AXID), as a Histamine H2-receptor antagonist, reduces gastric acid secretion and improves gastric motility function. Objectives : The effect of nizatidine using 150mg b.i.d was evaluated for symptom relief and improvement of laryngoscopic findings in patients with LPR. Materials and Methods : In 30 multicenter, observational trial performed nationalwidely in Korea. 308 patients with LPR symptom were observed to evaluate their symptoms and larygnoscopic findings after 4weeks, 8weeks, 12weeks of treatment with nizatidine. Results : The symptoms of LPR including globus sensation, chronic throat clearing and hoarseness, are reduced significantly after 4 weeks, 8weeks, and 12weeks of treatment(p<0.05). The laryngoscopic findings including diffuse erythema, edema and granulation are improved after nizatidine treatment(p<0.05). and the efficacy of nizatidine on LPR-related sympoms after 4 weeks is 88.6%, and those of after 8 weeks and 12weeks were 92.6%, and 99.1% in ITT(Intent To Treatment) group(p<0.05). And PPA(Per Protocol Analysis)group showed 93.7%, 97.3%, and 99.1% of efficacy after 4, 8, and 12 weeks of nizatidine treatment(p<0.05). Conclusion : These results indicate that in patient with LPR, nizatidine 150mg b.i.d treatment very effectively reduces LPR symptoms and improves laryngoscopic findings as well as reduces gastric acid secretion and improves gastric motility function.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.483-489
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• 2004

Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.