BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy can be the end-stage of severe cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly and heart failure (HF). Although a wide variety of animal models are available to study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy with non-invasive, simple, and large screening methods. METHODS: We developed a dilated cardiomyopathy model in zebrafish larvae using short duration terfenadine, a known cardiotoxic drug that induces ventricular size dilation. Fractional shortening of zebrafish hearts was calculated. RESULTS: We treated zebrafish with 5 to 10 µM terfenadine for 24 hours. In terfenadine-treated zebrafish, blood frequently pooled and clotted in the chamber, and circulation was remarkably reduced. Atria and ventricles were swollen, and fluid was deposited around the heart, mimicking edema. Cardiac contractility was significantly reduced, and ventricular area was significantly enlarged. Heart rate was markedly reduced even after terfenadine withdrawal. Acridine orange staining also showed that terfenadine increased cardiomyocyte apoptosis. A significant increase of natriuretic peptide B (NPPB) mRNA was found in terfenadine-treated zebrafish. A low dose of terfenadine (5–10 µM) did not show mortality in short-term treatment (24 hours). However, moderate dose (35–45 µM) terfenadine treatment reduced zebrafish survival within 1 hour. CONCLUSION: With advantages of rapid sample preparation procedure and transparent observation of the live heart, this model can potentially be applied to large-scale drug screening and toxicity assays for non-ischemic HF.
Acridine Orange ; Apoptosis ; Cardiomegaly ; Cardiomyopathies ; Cardiomyopathy, Dilated* ; Drug Evaluation, Preclinical ; Edema ; Heart ; Heart Failure ; Heart Rate ; Larva* ; Mass Screening ; Models, Animal ; Mortality ; Myocardium ; Myocytes, Cardiac ; RNA, Messenger ; Terfenadine* ; Zebrafish*

OBJECTIVETo establish a precolumn chiral derivatization method for determination of fexofenadine enantiomers, a chiral substrate of OATP1B1, in cellular model.

METHODSR-(+)-phenylethyl isocyanate was selected as chiral derivatization reagent, which was reacted with fexofenadine to form carbamate derivatives. Enantiomers were identified by LC/MS and separated by RP-HPLC.

RESULTSUnder the experimental conditions, the fexofenadine enantiomers were separated completely. The standard curve was linear over the concentration range of 25-100 ng/ml (R(2)=0.9992, 0.9989). Accuracy was 101.1% and 98.3%, intra-precision was 2.4% and 3.1%, inter-precision was 3.1% and 4.0% for D1 and D2, respectively.

CONCLUSIONThe method established is sensitive and accurate for determination of fexofenadine enantiomers in cells.

BACKGROUND: Montelukast is a type 1 cysteinyl-leukotrienes receptor antagonist that has been widely used in allergic disease. However, the effect of combination of leukotriene receptor antagonist and antihistamine is controversial. The aim of this study was to compare the effect of combination treatment of montelukast and antihistamine, fexofenadine, over antihistamine alone in patients with allergic rhinitis (AR). SUBJECTS AND METHODS: Retrospective chart review of 60 patients with AR was undertaken. Patients were classified into combination group (montelukast and fexofenadine, n=28) and antihistamine only group (fexofenadine, n=32) according to treatment modalities. Questionnaire survey was performed and allergic symptoms (VAS scale, 5pointscale), and SNOT (sinonasal outcome test)-20 score were obtained before and after the treatment. RESULTS: Mean follow-up duration was 6.7+/-4.6weeks. There was no significant difference in demographic data between two groups. Allergic symptoms and SNOT-20 score(nasal, QOL domain) were improved significantly in both groups after the treatment (all p < 0.001). Combination treatment group showed better improvement in nasal obstruction than antihistamine treatment group(p = 0.03). However, there were no significant differences in other allergic symptoms (rhinorrhea and sneezing) and SNOT-20 between two groups (all p > 0.05, respectively). CONCLUSION: A combination treatment of montelukast and fexofenadine showed more efficacies in nasal obstruction than single fexofenadine treatment in patients with AR. Therefore, montelukast could be used effectively with antihistamine in patients with AR complaining nasal congestion.
Acetates ; Estrogens, Conjugated (USP) ; Follow-Up Studies ; Humans ; Nasal Obstruction ; Quinolines ; Receptors, Leukotriene ; Retrospective Studies ; Rhinitis* ; Rhinitis, Allergic, Perennial ; Terfenadine ; Surveys and Questionnaires

Aquagenic urticaria is a rare form of physical urticaria, in which contact with water evokes wheals. A 19-year-old man and a 4-year-old boy complained of recurrent episodes of urticaria. Urticaria appeared while taking a bath or a shower, in the rain, or in a swimming pool. Well-defined pin head to small pea-sized wheals surrounded by variable sized erythema were provoked by contact with water on the face, neck, and trunk, regardless of its temperature or source. Results from a physical examination and a baseline laboratory evaluation were within normal limits. Treatment of the 19-year-old man with 180 mg fexofenadine daily was successful to prevent the wheals and erythema. Treatment with 5 ml ketotifen syrup bid per day resulted in improvement of symptoms in the 4-year-old boy.
Baths ; Erythema ; Head ; Humans ; Ketotifen ; Neck ; Physical Examination ; Preschool Child ; Rain ; Swimming Pools ; Terfenadine ; Urticaria ; Water ; Young Adult

Fexofenadine (Allegra(R) 180) is a second-generation antihistamine. It is widely used as anti-allergic drug, which suppresses various allergic reactions mediated by histamines. A few cases of H1-antihistamine-induced urticaria have been reported. Herein, we report a rare case of fexofenadine-induced urticaria which was confirmed by a prick test, oral provocation test, and flow cytometry assisted-basophil activation test.
Basophil Degranulation Test ; Flow Cytometry ; Hypersensitivity ; Terfenadine ; Urticaria

BACKGROUND: Fexofenadine (Allegra(R)) is a H1-receptor selective antihistamine which exhibits consistent efficacy and safety in the treatment of allergic diseases. We thought that fexofenadine may be useful in treatment of the pruritus associated with eczema. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of fexofenadine in the treatment of pruritus associated with eczema. METHODS: In this study, patients with atopic and allergic contact dermatitis were divided into a group given fexofenadine 180 mg once daily with topical prednicarbate treatment group or a topical prednicarbate treatment only group, for 1 week. The primary efficacy parameter was the mean change from baseline in pruritus score, and the secondary parameters were the mean change in the incidence of scratching, the mean change in visual analogue scale (0~100 mm) of pruritus, and a comparison of patient satisfaction. RESULTS: 435 patients were included and the mean age was 32.9 years old. The mean pruritus score at baseline was 3.55 point in fexofenadine group and 3.51 point in the control group. Regarding the mean change in pruritus score, fexofenadine significantly decreased the severity of pruritus compared with the control group (p<0.05). There were no significant differences in the decrease in the incidence of scratching between the two groups. A decrease in pruritus levels utilizing visual analogue scale was significant in the fexofenadine group (p<0.05) and patient satisfaction was significantly higher in the fexofenadine group (p=0.0192). There was no significant difference in the incidence of adverse events between two groups (p=0.6237). CONCLUSION: Fexofenadine administered 180 mg once daily in combination with topical prednicarbate treatment was effective and well tolerated in this study.
Dermatitis, Allergic Contact ; Dermatitis, Atopic ; Eczema ; Humans ; Incidence ; Patient Satisfaction ; Prednisolone ; Pruritus ; Terfenadine

PURPOSE: To estimate the prevalence of co-prescribing contraindicated drugs for elderly patients in Busan. METHODS: We used the Health Insurance Review Agency (HIRA) claims database. Study population consisted of elderly patients who visited clinics or hospitals in Busan metropolitan city from January 1, 2000 to December 31, 2001. Contraindicated drugs were defined as 162 combinations of contraindicated drugs announced by the Korea Ministry of Health and Welfare in 2004. The co-prescription of contraindicated drugs was defined as prescribing two or more contraindicated drugs in combination in the same prescription. The prevalence of co-prescribing contraindicated drugswas estimated as proportion of co-prescribed patients out of the study patients. We estimated and age-adjusted prevalence and its 95% confidence interval of co-prescription of contraindicated drugs among the elderly patients in Korean population in 2001. RESULTS: The study elderly patients were 262,952 with 2,483,227 prescriptions. Among the study patients 1,208 (4.6%) were prescribed contraindicated drugs in combination. A total of 16,255 patients were estimated as the number of co-prescribed patients among the Korean elderly in 2001. Age-standardized prevalence of co-prescription to the Korean elderly was estimated to be 45 per 10,000 persons. The most frequently prescribed combinations were cisapride & amitriptyline, roxithromycin & ergoloid mesylate, and terfenadine & erythromycin, and the frequency were 325 (16.8%), 149 (7.7%), and 132 (6.8%),respectively. CONCLUSIONS: The contraindicated drugs were co-prescribed to the elderly patients in Korea. Many of these co-prescriptions should be avoided if unnecessary. The patients should be carefully monitored if they were inevitably prescribed the contraindicated drugs.
Aged ; Amitriptyline ; Cisapride ; Drug Combinations ; Drug Utilization Review ; Ergoloid Mesylates ; Erythromycin ; Humans ; Insurance, Health ; Korea ; Prescriptions ; Prevalence ; Roxithromycin ; Terfenadine

The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H1 and H2 and that the selective H1 antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H2 antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of beta-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and beta-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth.
Animals ; Apoptosis ; Carcinoma, Hepatocellular/*metabolism/*pathology ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Cyclooxygenase 2/metabolism ; Enzyme Activation ; Exocytosis ; Female ; Histamine/*pharmacology ; Histamine Antagonists/pharmacology ; Humans ; Liver Neoplasms/*metabolism/*pathology ; Mast Cells/*physiology ; Microtubule-Associated Proteins/metabolism ; Neoplasm Proteins/metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Ranitidine/pharmacology ; Rats ; Rats, Wistar ; Receptors, Histamine/metabolism ; Terfenadine/pharmacology ; beta Catenin/metabolism

Animals ; Dose-Response Relationship, Drug ; Guinea Pigs ; Heart Ventricles ; Ion Channels ; antagonists & inhibitors ; physiology ; Male ; Myocytes, Cardiac ; drug effects ; physiology ; Promethazine ; pharmacology ; Terfenadine ; pharmacology ; Time Factors

Adolescent ; Adult ; Aged ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Prednisone ; therapeutic use ; Terfenadine ; therapeutic use