2,658 results on '"terfenadine"'
Search Results
2. Effect of Antihistamines on Ureteral Stent-Related Symptoms
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Coloplast A/S and Ojas Shah, George F. Cahill Professor of Urology
- Published
- 2024
3. Terfenadine, a histamine H1 receptor antagonist, induces apoptosis by suppressing STAT3 signaling in human colorectal cancer HCT116 cells.
- Author
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Manoj Kumar Baniya, Eun-Hee Kim, and Kyung-Soo Chun
- Subjects
HISTAMINE receptors ,ANTIHISTAMINES ,COLORECTAL cancer ,CANCER cells ,STAT proteins ,APOPTOSIS ,RAS oncogenes - Abstract
Introduction: Colorectal cancer is a highly aggressive and metastatic cancer with inadequate clinical outcomes. Given the crucial role of histamine and histamine receptors in colorectal carcinogenesis, this study aimed at exploring the anticancer effects of terfenadine against colorectal cancer HCT116 cells and elucidate its underlying mechanism. Methods: Herein, we examined the effect of terfenadine on growth and proliferation of HCT116 cells in vitro and in vivo. Various experimental techniques such as flow cytometry, western blot, immunoprecipitation, luciferase assay were employed to unveil the mechanism of cell death triggered by terfenadine. Results: Terfenadine markedly attenuated the viability of HCT116 cells by abrogating histamine H1 receptor (H1R) signaling. In addition, terfenadine modulated the balance of Bax and Bcl-2, triggering cytochrome c discharge in the cytoplasm, thereby stimulating the caspase cascade and poly-(ADP-ribose) polymerase (PARP) degradation. Moreover, terfenadine suppressed murine double minute-2 (Mdm2) expression, whereas p53 expression increased. Terfenadine suppressed STAT3 phosphorylation and expression of its gene products by inhibiting MEK/ERK and JAK2 activation in HCT116 cells. Furthermore, treatment with U0126, a MEK inhibitor, and AG490, a JAK2 inhibitor, dramatically diminished the phosphorylations of ERK1/2 and JAK2, respectively, leading to STAT3 downregulation. Likewise, terfenadine diminished the complex formation of MEK1/2 with β-arrestin 2. In addition, terfenadine dwindled the phosphorylation of PKC substrates. Terfenadine administration (10 mg/kg) substantially retarded the growth of HCT116 tumor xenografts in vivo. Conclusion: Terfenadine induces the apoptosis of HCT116 cells by abrogating STAT3 signaling. Overall, this study supports terfenadine as a prominent anticancer therapy for colorectal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
4. Excipient Effect on Drug Absorption in Humans
- Author
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Food and Drug Administration (FDA)
- Published
- 2023
5. Torsade de pointes associated with long-term antiretroviral drugs in a patient with HIV: a case report.
- Author
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Xuechun Mu, Yujiao Duan, Qiuhua Xu, Sa Wang, Guiju Gao, Ning Han, and Hongxin Zhao
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ANTI-HIV agents ,ANTIRETROVIRAL agents ,HIV ,CYTOCHROME P-450 CYP3A ,RITONAVIR ,ATAZANAVIR ,DRUG interactions ,LOSS of consciousness - Abstract
With the improving life expectancy of patients with human immunodeficiency virus (HIV), there is an increasing health concern of potential toxicity and drug interactions of long-term antiretroviral therapies. We describe a female patient with HIV, who was admitted to the emergency department following an unexplained loss of consciousness. This patient had been on antiretroviral therapy comprising tenofovir disoproxil fumarate, lamivudine, and lopinavir/ ritonavir for 12 years. Coincidentally, she had been prescribed terfenadine for urticaria recently. After 3 days on this medication, she suddenly lost her consciousness, with a distinctive electrocardiogram alteration characterized by QT prolongation and torsade de pointes. This symptom recurred several times over a span of 2 days. We postulate that the primary instigator was an elevated concentration of terfenadine, which can be traced back to her antiretroviral therapy regimen comprising lopinavir/ritonavir. This drug is known to impede the metabolism of cytochrome P450 3A4 substrates and consequently elevate terfenadine concentrations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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6. Repurposing Terfenadine as a Novel Antigiardial Compound.
- Author
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Suárez-Rico, Daniel Osmar, Munguía-Huizar, Francisco Javier, Cortés-Zárate, Rafael, Hernández-Hernández, José Manuel, González-Pozos, Sirenia, Perez-Rangel, Armando, and Castillo-Romero, Araceli
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GIARDIA lamblia , *DRUG repositioning , *GIARDIASIS , *DRUG development , *DRUG resistance , *TUBULINS , *CELL survival - Abstract
Giardia lamblia is a highly infectious protozoan that causes giardiasis, a gastrointestinal disease with short-term and long-lasting symptoms. The currently available drugs for giardiasis treatment have limitations such as side effects and drug resistance, requiring the search for new antigiardial compounds. Drug repurposing has emerged as a promising strategy to expedite the drug development process. In this study, we evaluated the cytotoxic effect of terfenadine on Giardia lamblia trophozoites. Our results showed that terfenadine inhibited the growth and cell viability of Giardia trophozoites in a time–dose-dependent manner. In addition, using scanning electron microscopy, we identified morphological damage; interestingly, an increased number of protrusions on membranes and tubulin dysregulation with concomitant dysregulation of Giardia GiK were observed. Importantly, terfenadine showed low toxicity for Caco-2 cells, a human intestinal cell line. These findings highlight the potential of terfenadine as a repurposed drug for the treatment of giardiasis and warrant further investigation to elucidate its precise mechanism of action and evaluate its efficacy in future research. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. Terfenadine
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Pant, AB
- Published
- 2024
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8. Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
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Zou, Ling, Spanogiannopoulos, Peter, Pieper, Lindsey M, Chien, Huan-Chieh, Cai, Wenlong, Khuri, Natalia, Pottel, Joshua, Vora, Bianca, Ni, Zhanglin, Tsakalozou, Eleftheria, Zhang, Wenjun, Shoichet, Brian K, Giacomini, Kathleen M, and Turnbaugh, Peter J
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Nutrition ,Digestive Diseases ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Oral and gastrointestinal ,ATP Binding Cassette Transporter ,Subfamily B ,Animals ,Anti-Allergic Agents ,Azo Compounds ,Bacteria ,Excipients ,Female ,Food ,Food Additives ,Gastrointestinal Microbiome ,Histamine H1 Antagonists ,Non-Sedating ,Humans ,Intestinal Absorption ,Male ,Mice ,Mice ,Inbred BALB C ,Mice ,Knockout ,Organic Anion Transporters ,Terfenadine ,excipients ,drug absorption ,human gut microbiome ,azoreductases ,food additives - Abstract
Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R-N=N-R') dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.
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- 2020
9. Findings from Federal Institute for Drugs and Medical Devices Broaden Understanding of Genomics and Genetics (Intracellular Binding of Terfenadine Competes With Its Access To Pancreatic B-cell Atp-sensitive K+ Channels and Human
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Medical equipment ,Terfenadine ,Genetic research ,Physiological apparatus ,Dofetilide ,Physical fitness ,Health - Abstract
2023 NOV 25 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on Genomics and Genetics have been published. According to [...]
- Published
- 2023
10. Intracellular Binding of Terfenadine Competes with Its Access to Pancreatic ß-cell ATP-Sensitive K+ Channels and Human ether-à-go-go-Related Gene Channels.
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Zünkler, Bernd J., Wos-Maganga, Maria, Bohnet, Stefanie, Kleinau, Anne, Manns, Detlef, and Chatterjee, Shivani
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HUMAN genes , *CHIMERIC proteins , *BINDING sites , *CONCENTRATION gradient , *FLUORESCENCE spectroscopy , *POTASSIUM channels - Abstract
Most blockers of both hERG (human ether-à-go-go-related gene) channels and pancreatic ß-cell ATP-sensitive K+ (KATP) channels access their binding sites from the cytoplasmic side of the plasma membrane. It is unknown whether binding to intracellular components competes with binding of these substances to K+ channels. The whole-cell configuration of the patch-clamp technique, a laser-scanning confocal microscope, and fluorescence correlation spectroscopy (FCS) were used to study hERG channels expressed in HEK (human embryonic kidney) 293 cells and KATP channels from the clonal insulinoma cell line RINm5F. When applied via the pipette solution in the whole-cell configuration, terfenadine blocked both hERG and KATP currents with much lower potency than after application via the bath solution, which was not due to P-glycoprotein-mediated efflux of terfenadine. Such a difference was not observed with dofetilide and tolbutamide. 37–68% of hERG/EGFP (enhanced green-fluorescent protein) fusion proteins expressed in HEK 293 cells were slowly diffusible as determined by laser-scanning microscopy in the whole-cell configuration and by FCS in intact cells. Bath application of a green-fluorescent sulphonylurea derivative (Bodipy-glibenclamide) induced a diffuse fluorescence in the cytosol of RINm5F cells under whole-cell patch-clamp conditions. These observations demonstrate the presence of intracellular binding sites for hERG and KATP channel blockers not dialyzable by the patch-pipette solution. Intracellular binding of terfenadine was not influenced by a mutated hERG (Y652A) channel. In conclusion, substances with high lipophilicity are not freely diffusible inside the cell but steep concentration gradients might exist within the cell and in the sub-membrane space. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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11. Terfenadine resensitizes doxorubicin activity in drugresistant ovarian cancer cells via an inhibition of CaMKII/CREB1 mediated ABCB1 expression.
- Author
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Wei Huang, Shu Yang, Yu-Shan Cheng, Ni Sima, Wei Sun, Min Shen, Braisted, John C., Weiguo Lu, and Wei Zheng
- Subjects
OVARIAN cancer ,P-glycoprotein ,DOXORUBICIN ,CANCER cells ,CYCLIC-AMP-dependent protein kinase ,MULTIDRUG resistance - Abstract
Ovarian cancer is one of the most lethal gynecological malignancies. Recurrence or acquired chemoresistance is the leading cause of ovarian cancer therapy failure. Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1), commonly known as P-glycoprotein, correlates closely with multidrug resistance (MDR). However, the mechanism underlying aberrant ABCB1 expression remains unknown. Using a quantitative high-throughput combinational screen, we identified that terfenadine restored doxorubicin sensitivity in an MDR ovarian cancer cell line. In addition, RNA-seq data revealed that the Ca2+-mediated signaling pathway in the MDR cells was abnormally regulated. Moreover, our research demonstrated that terfenadine directly bound to CAMKIID to prevent its autophosphorylation and inhibit the activation of the cAMP-responsive element-binding protein 1 (CREB1)- mediated pathway. Direct inhibition of CAMKII or CREB1 had the same phenotypic effects as terfenadine in the combined treatment, including lower expression of ABCB1 and baculoviral IAP repeat-containing 5 (BIRC5, also known as survivin) and increased doxorubicin-induced apoptosis. In this study, we demonstrate that aberrant regulation of the Ca2+-mediated CAMKIID/CREB1 pathway contributes to ABCB1 over-expression and MDR creation and that CAMKIID and CREB1 are attractive targets for restoring doxorubicin efficacy in ABCB1-mediated MDR ovarian cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Repurposing Terfenadine as a Novel Antigiardial Compound
- Author
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Daniel Osmar Suárez-Rico, Francisco Javier Munguía-Huizar, Rafael Cortés-Zárate, José Manuel Hernández-Hernández, Sirenia González-Pozos, Armando Perez-Rangel, and Araceli Castillo-Romero
- Subjects
Giardia lamblia ,terfenadine ,ion channels ,tubulin ,drug repurposing ,autophagy ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Giardia lamblia is a highly infectious protozoan that causes giardiasis, a gastrointestinal disease with short-term and long-lasting symptoms. The currently available drugs for giardiasis treatment have limitations such as side effects and drug resistance, requiring the search for new antigiardial compounds. Drug repurposing has emerged as a promising strategy to expedite the drug development process. In this study, we evaluated the cytotoxic effect of terfenadine on Giardia lamblia trophozoites. Our results showed that terfenadine inhibited the growth and cell viability of Giardia trophozoites in a time–dose-dependent manner. In addition, using scanning electron microscopy, we identified morphological damage; interestingly, an increased number of protrusions on membranes and tubulin dysregulation with concomitant dysregulation of Giardia GiK were observed. Importantly, terfenadine showed low toxicity for Caco-2 cells, a human intestinal cell line. These findings highlight the potential of terfenadine as a repurposed drug for the treatment of giardiasis and warrant further investigation to elucidate its precise mechanism of action and evaluate its efficacy in future research.
- Published
- 2023
- Full Text
- View/download PDF
13. Terfenadine resensitizes doxorubicin activity in drug-resistant ovarian cancer cells via an inhibition of CaMKII/CREB1 mediated ABCB1 expression
- Author
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Wei Huang, Shu Yang, Yu-Shan Cheng, Ni Sima, Wei Sun, Min Shen, John C. Braisted, Weiguo Lu, and Wei Zheng
- Subjects
drug-resistant ,ovarian cancer ,terfenadine ,CaMKII ,doxorubicin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Ovarian cancer is one of the most lethal gynecological malignancies. Recurrence or acquired chemoresistance is the leading cause of ovarian cancer therapy failure. Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1), commonly known as P-glycoprotein, correlates closely with multidrug resistance (MDR). However, the mechanism underlying aberrant ABCB1 expression remains unknown. Using a quantitative high-throughput combinational screen, we identified that terfenadine restored doxorubicin sensitivity in an MDR ovarian cancer cell line. In addition, RNA-seq data revealed that the Ca2+-mediated signaling pathway in the MDR cells was abnormally regulated. Moreover, our research demonstrated that terfenadine directly bound to CAMKIID to prevent its autophosphorylation and inhibit the activation of the cAMP-responsive element-binding protein 1 (CREB1)-mediated pathway. Direct inhibition of CAMKII or CREB1 had the same phenotypic effects as terfenadine in the combined treatment, including lower expression of ABCB1 and baculoviral IAP repeat-containing 5 (BIRC5, also known as survivin) and increased doxorubicin-induced apoptosis. In this study, we demonstrate that aberrant regulation of the Ca2+-mediated CAMKIID/CREB1 pathway contributes to ABCB1 over-expression and MDR creation and that CAMKIID and CREB1 are attractive targets for restoring doxorubicin efficacy in ABCB1-mediated MDR ovarian cancer.
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- 2022
- Full Text
- View/download PDF
14. A Study To Investigate The Safety And Toleration Of Multiple Oral Doses Of PF-03654764 In Combination With Fexofenadine In Healthy Subjects
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- 2019
15. Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels
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Delgado-Ramírez Mayra, Rodriguez-Leal Fanny Junue, Rodríguez-Menchaca Aldo Azmar, Moreno-Galindo Eloy Gerardo, Sanchez-Chapula José Antonio, and Ferrer Tania
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terfenadine ,inward rectifier potassium channels ,phosphatidylinositol 4,5-bisphosphate ,cationic amphiphilic drugs ,Pharmaceutical industry ,HD9665-9675 - Abstract
Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral processes. Hence, we characterized the effects of terfenadine on Kir2.x channels expressed in HEK-293 cells. Terfenadine inhibited Kir2.3 channels with a strikingly greater potency (IC50 = 1.06 ± 0.11 μmol L−1) compared to Kir2.1 channels (IC50 = 27.8 ± 4.8 μmol L−1). The Kir2.3(I213L) mutant, possessing a larger affinity for phosphatidylinositol 4,5-bisphosphate (PIP2) than the wild-type Kir2.3, was less sensitive to terfenadine inhibition (IC50 = 13.0 ± 2.9 μmol L−1). Additionally, the PIP2 intracellular application had largely reduced the inhibition of Kir2.1 channels by terfenadine. Our data support that Kir2.x channels are targets of terfena-dine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine.
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- 2021
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16. Potential Small Molecules for Therapy of Lupus Nephritis Based on Genetic Effect and Immune Infiltration.
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Qing, Jianbo, Song, Wenzhu, Tian, Lingling, Samuel, Sonia Biju, and Li, Yafeng
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SMALL molecules , *RESEARCH , *TERFENADINE , *LUPUS nephritis , *MACROPHAGES , *MEFLOQUINE , *IMMUNOSUPPRESSION , *BIOINFORMATICS , *INTERFERONS , *GENES , *STATISTICAL correlation , *PROCHLORPERAZINE , *MONOCYTES - Abstract
Lupus nephritis (LN) is the most common and significant complication of systemic lupus erythematosus (SLE) due to its poor prognosis and mortality rates in SLE patients. There is a critical need for new drugs as the pathogenesis of LN remains to be elucidated and immunosuppressive therapy comes with many deficiencies. In this study, 23 hub genes (IFI6, PLSCR1, XAF1, IFI16, IFI44, MX1, IFI44L, IFIT3, IFIT2, IFI27, DDX58, EIF2AK2, IFITM1, RTP4, IFITM3, TRIM22, PARP12, IFIH1, OAS1, HERC6, RSAD2, DDX60, and MX2) were identified through bioinformatics and network analysis and are closely related to interferon production and function. Interestingly, immune cell infiltration analysis and correlation analysis demonstrate a positive correlation between the expression of 23 hub genes and monocyte infiltration in glomeruli and M2 macrophage infiltration in the tubulointerstitium of LN patients. Additionally, the CTD database, DsigDB database, and DREIMT database were used to explore the bridging role of genes in chemicals and LN as well as the potential influence of these chemicals on immune cells. After comparison and discussion, six small molecules (Acetohexamide, Suloctidil, Terfenadine, Prochlorperazine, Mefloquine, and Triprolidine) were selected for their potential ability in treating lupus nephritis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
17. Single Crystal Structure of Terfenadine Form I.
- Author
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Bookwala, Mustafa, Gumireddy, Ashwini, Aitken, Jennifer A., and Wildfong, Peter L. D.
- Subjects
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CRYSTAL structure , *SINGLE crystals , *X-ray powder diffraction , *CRYSTALS , *DIFFERENTIAL scanning calorimetry - Abstract
Terfenadine, C32H41NO2, 1, contains an α,α-diphenyl-4-piperidinomethanol moiety, which is related to the H1-receptor blocking activity, facilitating its prior use as an antihistamine drug. In addition to its bioactivity, terfenadine is useful as a model, small-molecule crystalline solid for studying several material properties. Despite a history of therapeutic use, the absence of a crystal structure has limited current studies of the physicochemical behavior of this material. In the present manuscript, the elusive X-ray crystal structure of 1 was solved and refined at 296 K using single crystals grown from a co-solvent mixture of acetonitrile:methanol:ethanol (0.50:0.25:0.25). Terfenadine crystallizes in the monoclinic space group P21/n, and exhibits a chair conformation of the piperidine ring and a gauche conformation of the n-butyl chain. Hydrogen bonds between O–H⋯O and O–H⋯N, along with weak van der Waals interactions between C16–H16B⋯H16B'–C16' and C2–H2⋯H16A–C16A were confirmed using Hirshfeld-Surface analysis. Differential scanning calorimetry and X-ray powder diffraction confirmed that the crystal structure reported herein was that of the most thermodynamically stable monotropic polymorph of terfenadine (form I). The elusive single crystal structure of terfenadine is solved and refined. Characterization using differential scanning calorimetry and powder X-ray diffraction confirms the structure to be the thermodynamically most stable polymorph (form I). [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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18. Intracellular Binding of Terfenadine Competes with Its Access to Pancreatic ß-cell ATP-Sensitive K+ Channels and Human ether-à-go-go-Related Gene Channels
- Author
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Zünkler, Bernd J., Wos-Maganga, Maria, Bohnet, Stefanie, Kleinau, Anne, Manns, Detlef, and Chatterjee, Shivani
- Published
- 2023
- Full Text
- View/download PDF
19. Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure
- Author
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Hailian Quan, Gyu Chul Oh, Seung Hyeok Seok, and Hae-Young Lee
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heart failure ,angiotensin receptor blockers ,renin angiotensin system ,zebrafish ,terfenadine ,Medicine - Abstract
Background/Aims Angiotensin II in the failing heart initially helps to maintain cardiac output and blood pressure, but ultimately accelerates its deterioration. In this study, we established a model of arrhythmia-induced heart failure (HF) in zebrafish and investigated the role of renin-angiotensin-aldosterone system (RAAS) modulation by using an angiotensin II type 1 receptor blocker, fimasartan, through the assessment of cellular and physiologic responses, morbidity, and mortality. Methods HF was induced in zebrafish larvae by exposure to 20 μM terfenadine. Morphologic, physiologic, and functional parameters were assessed in the presence or absence of fimasartan treatment. Results Zebrafish exposed to terfenadine showed marked dilatation of the ventricle and reduced systolic function. Treatment with terfenadine was associated with 10-fold higher expression of atrial natriuretic peptide (p < 0.001 vs. vehicle), increased p53 mRNA expression, and chromatin fragmentation in the TUNEL assay, all of which were significantly reduced by fimasartan treatment. Moreover, fimasartan improved fractional shortening (terfenadine + fimasartan 16.9% ± 3.1% vs. terfenadine + vehicle 11.4% ± 5.6%, p < 0.05) and blood flow (terfenadine + fimasartan 479.1 ± 124.1 nL/sec vs. terfenadine + vehicle 273.0 ± 109.0 nL/sec, p < 0.05). Finally, treatment with fimasartan remarkably reduced mortality (terfenadine + fimasartan 36.0% vs. terfenadine + vehicle 96.0%, p < 0.001). Conclusions Fimasartan effectively protected against the progression of HF in zebrafish by improving hemodynamic indices, which improved survival. A reduction in apoptotic cell death and an improvement in hemodynamics may be the mechanisms behind these effects. Further human studies are warranted to evaluate the possible role of fimasartan in the treatment of HF.
- Published
- 2020
- Full Text
- View/download PDF
20. Drug repositioning: antiprotozoal activity of terfenadine against Entamoeba histolytica trophozoites.
- Author
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Rangel-Castañeda, Itzia Azucena, Castillo-Romero, Araceli, León-Ávila, Gloria, Zermeño-Ruiz, Martin, and Hernández-Hernández, José Manuel
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ENTAMOEBA histolytica , *DRUG repositioning , *TROPHOZOITES , *TRYPAN blue , *CELL survival - Abstract
The infection caused by Entamoeba histolytica is still a serious public health problem, especially in developing countries. The goal of this study was to evaluate the effect of terfenadine against Entamoeba histolytica. The trophozoites were exposed to 1, 2, 3, and 4 μM of terfenadine, for 24 and 48 h. Consequently, the viability of cells was determined by trypan blue exclusion test. The effect of terfenadine on adhesion of Entamoeba histolytica was evaluated in Caco-2 cells. In addition, the effect of terfenadine on the erythrophagocytic capacity of the parasite was investigated. The results show that terfenadine affects the growth and cell viability in a time- and dose-dependent manner. The higher inhibitory effects were observed with 4 µM at 48 h; 91.6% of growth inhibition and only 22.5% of trophozoites were viable. Additionally, we demonstrate that terfenadine is highly selective for the parasite and has low toxicity on Caco-2 cells. Furthermore, adhesion to Caco-2 cells and erythrophagocytic capacity were significantly inhibited. These findings demonstrate that terfenadine exerts significant effects on the virulence of Entamoeba histolytica. This is the first study demonstrating the amoebicidal activity of terfenadine and the results suggest it may be effective in the treatment of amoebiasis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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21. Terfenadine, a histamine H1 receptor antagonist, induces apoptosis by suppressing STAT3 signaling in human colorectal cancer HCT116 cells.
- Author
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Baniya MK, Kim EH, and Chun KS
- Abstract
Introduction: Colorectal cancer is a highly aggressive and metastatic cancer with inadequate clinical outcomes. Given the crucial role of histamine and histamine receptors in colorectal carcinogenesis, this study aimed at exploring the anticancer effects of terfenadine against colorectal cancer HCT116 cells and elucidate its underlying mechanism., Methods: Herein, we examined the effect of terfenadine on growth and proliferation of HCT116 cells in vitro and in vivo . Various experimental techniques such as flow cytometry, western blot, immunoprecipitation, luciferase assay were employed to unveil the mechanism of cell death triggered by terfenadine., Results: Terfenadine markedly attenuated the viability of HCT116 cells by abrogating histamine H1 receptor (H1R) signaling. In addition, terfenadine modulated the balance of Bax and Bcl-2, triggering cytochrome c discharge in the cytoplasm, thereby stimulating the caspase cascade and poly-(ADP-ribose) polymerase (PARP) degradation. Moreover, terfenadine suppressed murine double minute-2 (Mdm2) expression, whereas p53 expression increased. Terfenadine suppressed STAT3 phosphorylation and expression of its gene products by inhibiting MEK/ERK and JAK2 activation in HCT116 cells. Furthermore, treatment with U0126, a MEK inhibitor, and AG490, a JAK2 inhibitor, dramatically diminished the phosphorylations of ERK1/2 and JAK2, respectively, leading to STAT3 downregulation. Likewise, terfenadine diminished the complex formation of MEK1/2 with β-arrestin 2. In addition, terfenadine dwindled the phosphorylation of PKC substrates. Terfenadine administration (10 mg/kg) substantially retarded the growth of HCT116 tumor xenografts in vivo ., Conclusion: Terfenadine induces the apoptosis of HCT116 cells by abrogating STAT3 signaling. Overall, this study supports terfenadine as a prominent anticancer therapy for colorectal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baniya, Kim and Chun.)
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- 2024
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22. Fluticasone Furoate Nasal Spray Versus Oral Fexofenadine
- Published
- 2016
23. In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome
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Romero, Lucia, Trenor, Beatriz, Yang, Pei-Chi, Saiz, Javier, and Clancy, Colleen E
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Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease ,Rare Diseases ,Pediatric ,Congenital Heart Disease ,Cardiovascular ,Genetics ,4.1 Discovery and preclinical testing of markers and technologies ,2.1 Biological and endogenous factors ,Action Potentials ,Anti-Arrhythmia Agents ,Astemizole ,Cisapride ,Computer Simulation ,Gene Expression ,Genetic Predisposition to Disease ,Heart Ventricles ,Humans ,Ion Channel Gating ,Kinetics ,Long QT Syndrome ,Models ,Statistical ,Mutation ,Phenethylamines ,Potassium Channel Blockers ,Potassium Channels ,Voltage-Gated ,Protein Conformation ,Severity of Illness Index ,Sotalol ,Sulfonamides ,Terfenadine ,Mutations ,Drug-induced long-QT syndrome ,Drug-induced arrhythmias ,Computer modeling ,Potassium channels ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Biochemistry and cell biology ,Cardiovascular medicine and haematology ,Medical physiology - Abstract
Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed "in silico mutagenesis" by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical formulation of the M54T MiRP1 latent mutation and simulated a provocative test. In this setting, application of dofetilide dramatically amplified the predicted QT interval duration in the M54T hMiRP1 mutation compared to wild-type.
- Published
- 2014
24. A Study of Onset of Action of Loratadine and Fexofenadine in Participants With Seasonal Allergic Rhinitis (P08712)
- Published
- 2015
25. Topical Treatment of Under Eye Dark Circles and Swelling
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TKL Research, Inc.
- Published
- 2015
26. A Study to Test a New Decongestant in Patients With Allergic Rhinitis Following a Nasal Allergen Challenge
- Published
- 2014
27. Cubosomes for Enhancing Intestinal Absorption of Fexofenadine Hydrochloride: In situ and in vivo Investigation
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Amal A Sultan, Nourhan F El Nashar, Shimaa M Ashmawy, and Gamal El Maghraby
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Organic Chemistry ,Biophysics ,Pharmaceutical Science ,Bioengineering ,Poloxamer ,General Medicine ,Rats ,Biomaterials ,Drug Liberation ,Intestinal Absorption ,International Journal of Nanomedicine ,Drug Discovery ,Animals ,Rabbits ,Terfenadine ,Particle Size - Abstract
Amal A Sultan, Nourhan F El Nashar, Shimaa M Ashmawy, Gamal M El Maghraby Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, EgyptCorrespondence: Amal A Sultan, Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt, Tel +20403336007, Fax +20403335466, Email amal.sultan@pharm.tanta.edu.egPurpose: The aim of this work was to probe cubosomes for enhanced intestinal absorption and oral bioavailability of poorly absorbable fexofenadine HCl (FEX-HCl).Materials and Methods: Two cubosomal systems were fabricated utilizing glyceryl mono-oleate, a lyotropic mono lamellar lipid as oil phase and poloxamer407 as stabilizer at weight ratios of 8:2 and 7:3. The morphology of cubosomes was researched using transmission electron microscopy (TEM) and particle size was measured using photon correlation spectroscopy. FEX-HCl release was monitored in vitro. The effect of cubosomal encapsulation on intestinal absorption was assessed using in situ rabbit intestinal perfusion technique. Carrageenan induced rat paw edema model was utilized to monitor in vivo anti-inflammatory effect before and after cubosomal encapsulation.Results: TEM revealed the existence of spherical and polygonal nanostructures arranged in honeycomb organization. Size measurement reflected nanoparticles with reduced size at higher poloxamer concentration. Release studies revealed liberation of FEX-HCl from cubosomes based on Higuchi kinetics model. The intestinal permeability data indicated incomplete absorption of FEX-HCl from simple aqueous solution with P-glycoprotein efflux contributing to this poor intestinal absorption. Incorporation of FEX-HCl in cubosomes enhanced membrane transport parameters. The intestinal absorption did not correlate with drug release suggesting that drug release is not the rate limiting with possible intact cubosomal transport. Cubosomal encapsulation of FEX-HCl significantly enhanced its in vivo anti-inflammatory efficacy compared to the aqueous FEX-HCl dispersion.Conclusion: Cubosomes are promising novel carriers for enhancing intestinal absorption of FEX-HCl. Intact FEX-HCl-cubosomal absorption is possible via trans-lymphatic pathway but this requires further investigations.Graphical Abstract: Keywords: fexofenadine, cubosomes, release kinetics, in situ perfusion, correlation
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- 2022
28. When Enough Is Now Too Much : Fatal Forty DDI: midazolam, itraconazole, CYP3A4
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Wittwer, Erica D., Sprung, Juraj, Nicholson, Wayne T., Marcucci, Catherine, editor, Hutchens, Michael P., editor, Wittwer, Erica D., editor, Weingarten, Toby N., editor, Sprung, Juraj, editor, Nicholson, Wayne T., editor, Lalwani, Kirk, editor, Metro, David G., editor, Dull, Randal O., editor, Swide, Christopher E., editor, Seagull, F. Jacob, editor, Kirsch, Jeffrey R., editor, and Sandson, Neil B., editor
- Published
- 2015
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29. Heart-Stopping Treatment : Fatal Forty DDI: verapamil, erythromycin, CYP3A4
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Wittwer, Erica D., Weingarten, Toby N., Sprung, Juraj, Marcucci, Catherine, editor, Hutchens, Michael P., editor, Wittwer, Erica D., editor, Weingarten, Toby N., editor, Sprung, Juraj, editor, Nicholson, Wayne T., editor, Lalwani, Kirk, editor, Metro, David G., editor, Dull, Randal O., editor, Swide, Christopher E., editor, Seagull, F. Jacob, editor, Kirsch, Jeffrey R., editor, and Sandson, Neil B., editor
- Published
- 2015
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30. Fexofenadine HCL - Pseudoephedrine HCL Combination Versus Allegra in Patients With Seasonal Allergic Rhinitis
- Published
- 2013
31. Methods Employed in Cytofluorometric Assessment of Eryptosis, the Suicidal Erythrocyte Death
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Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, and Florian Lang
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Ceramide ,Glutathion ,Caspases ,Kinases ,NSC-95397 ,Bi-2536 ,Fascaplycin ,Lopinavir ,Terfenadine ,RBC ,Calcium ,Cell volume ,Cell membrane scrambling ,ROS ,Fucoxanthin ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins. Eryptosis is characterized by cell membrane scrambling with phosphatidylserine exposure to the erythrocyte surface. Triggers of eryptosis include oxidative stress, hyperosmotic shock, and energy depletion. Signalling involved in the regulation of eryptosis includes Ca2+ entry, ceramide, caspases, calpain, p38 kinase, protein kinase C, Janus-activated kinase 3, casein kinase 1α, cyclin-dependent kinase 4, AMP-activated kinase, p21-activated kinase 2, cGMP-dependent protein kinase, mitogen- and stress-activated kinase MSK1/2, and ill-defined tyrosine kinases. Inhibitors of eryptosis may prevent anaemia in clinical conditions associated with enhanced eryptosis and stimulators of eryptosis may favourably influence the clinical course of malaria. Additional experimentation is required to uncover further clinical conditions with enhanced eryptosis, as well as further signalling pathways, further stimulators, and further inhibitors of eryptosis. Thus, a detailed description of the methods employed in the analysis of eryptosis may help those, who enter this exciting research area. The present synopsis describes the experimental procedures required for the analysis of phosphatidylserine exposure at the cell surface with annexin-V, cell volume with forward scatter, cytosolic Ca2+ activity ([Ca2+]i) with Fluo3, oxidative stress with 2′,7′-dichlorodihydrofuorescein diacetate (DCFDA), glutathione (GSH) with mercury orange 1(4-chloromercuryphenyl-azo-2-naphthol), lipid peroxidation with BODIPY 581/591 C11 fluorescence, and ceramide abundance with specific antibodies. The contribution of kinases and caspases is defined with the use of the respective inhibitors. It is hoped that the present detailed description of materials and methods required for the analysis of eryptosis encourages further scientists to enter this highly relevant research area.
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- 2017
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32. Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.
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Ximenez JPB, de Andrade JM, Rocha A, Barbosa Coelho E, Suarez-Kurtz G, and Lanchote VL
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- Humans, Female, Postmenopause, Terfenadine, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Breast Neoplasms
- Abstract
Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUC
inf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2024
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33. Researchers from National Polytechnic Institute Discuss Findings in Terfenadine Therapy (Drug Repositioning: Antiprotozoal Activity of Terfenadine Against Entamoeba Histolytica Trophozoites)
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Terfenadine ,Physical fitness ,Health - Abstract
2021 DEC 11 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on Drugs and Therapies - Terfenadine Therapy have been [...]
- Published
- 2021
34. The Allegra transcatheter heart valve: Long-term clinical and echocardiographic outcomes.
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Wolfrum M, Moccetti F, Conrad N, Loretz L, Bossard M, Attiger-Toller A, Cuculi F, and Toggweiler S
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- Humans, Animals, Cattle, Female, Aged, Aged, 80 and over, Male, Terfenadine, Catheters, Heart Valves, Echocardiography
- Abstract
Objectives: The Allegra-THV is a novel, self-expanding THV with supra-annular bovine leaflets. The valve is available in 3 different sizes and is delivered through an 18 French sheath. To determine the safety and efficacy of the Allegra transcatheter heart valve (THV; Biosensors) for the treatment of severe aortic valve stenosis under real-world conditions., Methods: Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) at the Heart-Centre Lucerne with the Allegra-THV were included. Echocardiographic data were collected at baseline, before discharge, and at 1-year follow-up; clinical outcomes were recorded for up to 3 years. Clinical endpoints were defined according to the definitions of the Valve-Academic-Research-Consortium., Results: One hundred-three patients (age 81 ± 7 years, 63% women) were enrolled. Median European System for Cardiac Operative Risk Evaluation II score was 4.1% (IQR 1.8%-4.2%). Mean aortic valve gradient was 6.9 ± 3.3 mm Hg and 7.7 ± 3.3 mm Hg, and an effective orifice area was 2.1 ± 0.5 cm2 and 2.0 ± 0.5 cm2 at 30 days and 1-year follow-up, respectively. More than mild paravalvular leak was observed in 2.0% of patients at 30 days and 3.3% at 1 year. At 1-year follow-up, 14.7% of patients required implantation of a new permanent pacemaker, 1 patient had endocarditis with an uneventful clinical course and good THV-function after antibiotic therapy, and no thrombosis, structural-valve-detoriation (SVD), or non-SVD had occurred. At 3-year follow-up, rates of all-cause and cardiovascular mortality were 31.4% and 18.8%, respectively., Conclusions: Transfemoral implantation of the Allegra-THV resulted in favorable clinical and echocardiographic outcomes at up to 3-year follow-up. Head-to-head randomized clinical trials are necessary to determine if the Allegra-THV valve performs as well as current generation valves.
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- 2023
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35. Grapefruit Juice and Some Oral Drugs: A Bitter Combination
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Vu, Minh Chau
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Citrus ,Terfenadine ,Felodipine ,Cytochrome P-450 - Abstract
Grapefruit juice has been found to interact with many oral drugs when taken concomitantly. Studies have shown that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4)- an important enzyme involved in drug metabolism- via mechanism-based inactivation. Drug elimination is therefore prevented, and as a result, the bioavailability of many orally administered drugs is substantially increased when the patient ingests grapefruit juice. The grapefruit-drug interaction may result in severe side effects, ranging from hypotension to fatal cardiac arrhythmias. The active ingredients in grapefruit juice are substances of the coumarin family, primarily 6'7'-dihydroxybergamottin (DHB), a compound that inhibits CYP3A4 by causing irreversible inactivation of the enzyme. A flavenoid, naringenin, is also though to play a minor role. Furthermore, the effects of grapefruit juice can last over 24 hours since last consumption. Because many drugs, including felodipine, terfenadine, cyclosporine, and saquinavir, are metabolized by CYP3A4, it is very important to be aware of the potential side effects if grapefruit juice is consumed while patients are on medications that are metabolized by this enzyme.
- Published
- 1999
36. The Effect Of PF-03654764 +/- Allegra On Symptoms Of Allergic Rhinitis
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Director, Clinical Trial Disclosure Group
- Published
- 2010
37. Pharmacometrics in Cardiovascular Safety
- Author
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Parkinson, Joanna, Chain, Anne S.Y., van der Graaf, Piet H., Visser, Sandra A.G., Crommelin, Daan J. A., Editor-in-chief, Lipper, Robert A., Editor-in-chief, Schmidt, Stephan, editor, and Derendorf, Hartmut, editor
- Published
- 2014
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38. Summary of Torsades de Pointes (TdP) Reports Associated with Intravenous Drug Formulations Containing the Preservative Chlorobutanol.
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Woosley, R. David, Romero, Klaus, Heise, Craig W., Gallo, Tyler, Tate, Jared, and Woosley, Raymond L.
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- *
DRUG side effects , *VENTRICULAR arrhythmia , *ELECTROCARDIOGRAPHY , *METHADONE hydrochloride , *TERFENADINE , *INTRAVENOUS therapy - Abstract
Introduction: Drug-induced torsades de pointes (TdP) is a potentially lethal ventricular arrhythmia that is associated with drugs that prolong the QT interval on the electrocardiogram (ECG) due to their interference with the cardiac potassium current, IKR. Intravenous (IV) formulations of methadone have been associated with TdP and contain the preservative chlorobutanol, which, like methadone, blocks IKR. The combinations of chlorobutanol with methadone or terfenadine, another IKR blocker, produce synergistic IKR block.Objective: The aim of this study was to examine and summarize the evidence available to address the question: what other IV drug formulations contain chlorobutanol and are they associated with TdP?Methods: IV drug products containing the preservative chlorobutanol were identified by searching the websites DailyMed ( https://dailymed.nlm.nih.gov/dailymed/index.cfm ) and Drugs@FDA ( https://www.accessdata.fda.gov/scripts/cder/daf/ ). For each drug identified, PubMed and the FDA's Adverse Event Reporting System (FAERS) were searched for reports of TdP and/or QT prolongation and FAERS data were analyzed for disproportionality of reports.Results: The search found nine drugs (methadone, epinephrine, papaverine, oxytocin, vasopressin, testosterone, estradiol, isoniazid, and desmopressin) that contain chlorobutanol 2.5 (n = 1) or 5.0 mg/mL. All nine drugs had reports of QT prolongation or TdP reported in FAERS and all but estradiol, testosterone, desmopressin, and isoniazid had reports of QT prolongation or TdP in PubMed. Two of the nine drugs (epinephrine and methadone) had positive signals (by disproportionality analysis) for TdP in FAERS (EB05 2.88 and 23.81, respectively) and four (methadone, epinephrine, papaverine, and vasopressin) were reported in published articles as the suspect drugs in cases of TdP.Conclusion: The pharmacologic profile of chlorobutanol (synergistic IKR block) and its association with reports of TdP and QT prolongation suggest the need for a full evaluation of its cardiac safety when used as a preservative in IV drug and vitamin formulations. [ABSTRACT FROM AUTHOR]- Published
- 2019
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39. Daurinoline suppressed the migration and invasion of chemo-resistant human non-small cell lung cancer cells by reversing EMT and Notch-1 and sensitized the cells to Taxol.
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Li, Dan-Dan, Qin, Xiao-Chun, Yang, Yue, Chu, Hai-Xiao, Li, Ruo-Lan, Ma, Ling-xiang, Ding, Huai-Wei, and Zhao, Qing-Chun
- Subjects
- *
NON-small-cell lung carcinoma , *PACLITAXEL , *METASTASIS , *TERFENADINE , *CISPLATIN - Abstract
Highlights • Daurinoline restore the sensitivity of resistant NSCLC cells was firstly found. • Daurinoline inhibite the migration and invasion of resistant NSCLC cells. • The anti-proliferation and anti-metastasis effects are related to EMT and Notch1. • We firstly found that daurinoline sensitizes chemo-resistant NSCLC cells to taxol. Abstract Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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40. The exploration of effect of terfenadine on Ca2+ signaling in renal tubular cells.
- Author
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Cheng, He-Hsiung, Liang, Wei-Zhe, Kuo, Chun-Chi, Hao, Lyh-Jyh, Chou, Chiang-Ting, and Jan, Chung-Ren
- Abstract
Terfenadine, an antihistamine used for the treatment of allergic conditions, affected Ca
2+ -related physiological responses in various models. However, the effect of terfenadine on cytosolic free Ca2+ levels ([Ca2+ ]i ) and its related physiology in renal tubular cells is unknown. This study examined whether terfenadine altered Ca2+ signaling and caused cytotoxicity in Madin–Darby canine kidney (MDCK) renal tubular cells. The Ca2+ -sensitive fluorescent dye fura-2 was used to measure [Ca2+ ]i . Cell viability was measured by the fluorescent reagent 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay. Terfenadine at concentrations of 100–1000 μM induced [Ca2+ ]i rises concentration dependently. The response was reduced by approximately 35% by removing extracellular Ca2+ . In Ca2+ -free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) partly inhibited terfenadine-evoked [Ca2+ ]i rises. Conversely, treatment with terfenadine abolished BHQ-evoked [Ca2+ ]i rises. Inhibition of phospholipase C (PLC) with U73122 inhibited 95% of terfenadine-induced Ca2+ release. Terfenadine-induced Ca2+ entry was supported by Mn2+ -caused quenching of fura-2 fluorescence. Terfenadine-induced Ca2+ entry was partly inhibited by an activator of protein kinase C (PKC), phorbol 12-myristate 13 acetate (PMA) and by three modulators of store-operated Ca2+ channels (nifedipine, econazole, and SKF96365). Terfenadine at 200–300 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in MDCK cells, terfenadine induced [Ca2+ ]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Furthermore, terfenadine caused cell death that was not triggered by preceding [Ca2+ ]i rises. [ABSTRACT FROM AUTHOR]- Published
- 2019
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41. An Efficient and Scalable Synthesis of Fexofenadine Hydrochloride.
- Author
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Castaldi, Michele, Baratella, Marco, Gaboardi, Mauro, Castaldi, Graziano, and Giovenzana, Giovanni B.
- Abstract
Allergic rhinitis (AR) is an important allergic inflammatory disease, affecting 30‐60 million people annually in the USA. The most important class of drug used in the treatment of AR is second‐generation H1‐antihistamines (highly selective and non‐sedating drugs) like levocetirizine, desloratadine and fexofenadine. Different synthetic strategies are reported for the preparation of fexofenadine hydrochloride, but these approaches involve the formation of byproducts, either toxic or difficult to remove. The aim of this work is to find a new, efficient and scalable synthetic approach for the preparation of fexofenadine hydrochloride. The final product was assembled from methyl 2‐(4‐bromophenyl)‐2‐methylpropanoate, 3‐butyn‐1‐ol and azacyclonol, cheap and commercially available raw materials. A key step allows to build the central oxygenated‐C4‐moiety through a key 5‐membered intermediate, avoiding toxic or expensive reagents and catalysts. The 8‐step synthesis is competitive with existing protocols, leading to fexofenadine hydrochloride in 59% overall yield. An alternative synthesis of fexofenadine starting from readily available and cheap starting materials was developed. The 8‐step synthesis allowed to obtain fexofenadine in 59% overall yield on a >100g scale and was easily adapted to the preparation of the cognate API terfenadine. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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42. ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral Cochlear Nucleus.
- Author
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Yildirim, Caner and Bal, Ramazan
- Subjects
- *
ELECTROPHYSIOLOGY , *NEURONS , *SODIUM channels , *ION channels , *TERFENADINE , *ACTION potentials , *ANIMAL experimentation , *AUTONOMIC ganglia , *BIOLOGICAL transport , *BRAIN stem , *CARRIER proteins , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *MICE , *PIPERIDINE , *PYRIDINE , *RESEARCH , *EVALUATION research , *NEURAL pathways , *PHARMACODYNAMICS - Abstract
ERG (ether-a-go-go-related gene) channels are the members of the voltage-dependent potassium channel family, which have three subtypes, as ERG1 (Kv 11.1), ERG2 (Kv 11.2), and ERG3 (Kv11.3). There is no information on ERG channels in the cochlear nucleus (CN) neurons, which is the first relay station of the auditory pathway. As occur in some of congenital long QT Syndromes (LQTS), mutation of the KCNQ11 genes for ERG channel has been reported to be accompanied by hearing loss. For that reason, we aimed to study biophysical properties and physiological importance, and contribution of ERG K+ currents to the formation of action potentials in the stellate and bushy neurons of the ventral cochlear nucleus (VCN). A total of 70 mice at 14-17 days old were used for this study. Electrophysiological characterization of ERG channels was performed using patch-clamp technique in the CN slices. In current clamp, ERG channel blockers, terfenadine (10 µM) and E-4031 (10 µM), were applied in both cell types. The activation, inactivation, and deactivation kinetics of the ERG channels were determined by voltage clamp. In conclusion, the findings obtained in the present study suggest that stellate and bushy neurons express ERG channels and ERG channels appear to contribute to setting action potential (AP) frequency, threshold for AP induction, and, possibly, resting membrane potentials in this cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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43. Findings from Federal Institute for Drugs and Medical Devices Broaden Understanding of Genomics and Genetics (Intracellular Binding of Terfenadine Competes With Its Access To Pancreatic B-cell Atp-sensitive K+ Channels and Human.
- Subjects
MEDICAL equipment ,GENETICS ,GENOMICS ,BINDING sites ,RESEARCH personnel ,POTASSIUM antagonists - Abstract
A recent study conducted in Bonn, Germany, has provided new insights into the field of Genomics and Genetics. The research focused on the binding of substances to hERG channels and pancreatic beta-cell ATP-sensitive K+ (K-ATP) channels. The study found that terfenadine, a commonly used medication, blocked both types of channels with lower potency when applied via the pipette solution compared to the bath solution. The researchers also discovered the presence of intracellular binding sites for these channel blockers. This research contributes to a better understanding of the mechanisms involved in cellular processes. [Extracted from the article]
- Published
- 2023
44. Stimulating Effect of Terfenadine on Erythrocyte Cell Membrane Scrambling
- Author
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Elena Signoretto, Michela Castagna, Abdulla Al Mamun Bhuyan, and Florian Lang
- Subjects
Phosphatidylserine ,Ionomycin ,Eryptosis ,Calcium ,Terfenadine ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: The antihistaminic drug Terfenadine may trigger apoptosis of tumor cells, an effect unrelated to its effect on histamine receptors. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling triggering eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, and ceramide. The present study explored, whether Terfenadine is capable to trigger eryptosis. Methods: Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence, and ceramide abundance at the human erythrocyte surface utilizing specific antibodies. Hemolysis was quantified from haemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Terfenadine (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells and triggered hemolysis without significantly modifying the average forward scatter. Terfenadine (7.5 µM) significantly increased Fluo3-fluorescence, but did not significantly modify DCF fluorescence or ceramide abundance. The effect of Terfenadine on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca2+. Exposure of human erythrocytes to Ca2+ ionophore ionomycin (1 µM, 15 min) triggered annexin-V-binding, an effect augmented by Terfenadine pretreatment (10 µM, 48 hours). Conclusions: Terfenadine triggers phospholipid scrambling of the human erythrocyte cell membrane, an effect in part due to entry of extracellular Ca2+ and in part due to sensitizing human erythrocyte cell membrane scrambling to Ca2+.
- Published
- 2016
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45. Transfermoral transcatheter aortic valve implantation using self-expanding Allegra bioprosthesis: One-year single-center outcomes
- Author
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Radosław Targoński, Romuald Lango, Aleksandra Stańska, Joanna Milan, Marcin Fijałkowski, Miłosz Jaguszewski, Dariusz Jagielak, Mirosław Gozdek, and Mariusz Kowalewski
- Subjects
medicine.medical_specialty ,New York Heart Association Class ,Transcatheter aortic ,Hemodynamics ,Prosthesis Design ,Single Center ,Transcatheter Aortic Valve Replacement ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Allegra ,Stroke ,transcatheter aortic valve implantation ,Aged ,Bioprosthesis ,business.industry ,Aortic Valve Stenosis ,General Medicine ,medicine.disease ,Interventional Cardiology ,Treatment Outcome ,Aortic Valve ,Heart Valve Prosthesis ,Aortic valve stenosis ,Cardiology ,Original Article ,Female ,NAUTILUS clinical study ,Terfenadine ,Cardiology and Cardiovascular Medicine ,business ,Atrioventricular block - Abstract
Background The NAUTILUS study aimed to evaluate the safety and performance of the Allegra bioprosthesis in high-risk recipients undergoing transcatheter aortic valve implantation and previously reported 30-day outcomes. In the current investigation 1-year results of the trial are presented. Methods Twenty-seven recipients with severe, symptomatic aortic valve stenosis at high surgical risk, who underwent treatment using the next-generation self-expanding Allegra via transfemoral approach were prospectively enrolled. Clinical endpoints assessed were: mortality, stroke, permanent pacemaker implantation, New York Heart Association class and re-hospitalizations. Prosthetic valve performance evaluation comprised of: mean gradient, effective orifice area and paravalvular leak. Results Patients were elderly (82.8 ± 4.2 years) and predominantly female (n = 19, 70.4%). All of them were deemed to be at high surgical risk with a mean logistic EuroSCORE of 12.5 ± 6.7. The bioprosthesis was successfully implanted in 92.6% of the cases (n = 25). At 1-year, all-cause mortality was 12.0% (n = 3) and stroke was 4.0% (n = 1). Three (12%) of patients developed complete atrioventricular block and received permanent pacemakers. 84% of patients were in New York Heart Association class II or lower. Need for subsequent hospitalization arose in 48% patients. The echocardiographic assessment confirmed an acceptable hemodynamic profile of the Allegra with low mean transprosthetic gradient (9.5 ± 3.4 mmHg), absence of severe paravalvular leak and a 20%-presence of moderate paravalvular leak. Conclusions The current follow-up observation study shows that the Allegra was associated with a satisfactory safety profile and hemodynamic performance at 1-year after implantation.
- Published
- 2021
46. Drug repositioning: antiprotozoal activity of terfenadine against Entamoeba histolytica trophozoites
- Author
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Araceli Castillo-Romero, José Manuel Hernández-Hernández, Gloria León-Ávila, Martin Zermeño-Ruiz, and Itzia Azucena Rangel-Castañeda
- Subjects
medicine.drug_class ,Virulence ,Pharmacology ,chemistry.chemical_compound ,Entamoeba histolytica ,parasitic diseases ,medicine ,Animals ,Humans ,Parasite hosting ,Terfenadine ,Trophozoites ,Amoebiasis ,Viability assay ,General Veterinary ,biology ,Drug Repositioning ,General Medicine ,medicine.disease ,biology.organism_classification ,Infectious Diseases ,chemistry ,Insect Science ,Antiprotozoal ,Parasitology ,Caco-2 Cells ,Growth inhibition ,medicine.drug - Abstract
The infection caused by Entamoeba histolytica is still a serious public health problem, especially in developing countries. The goal of this study was to evaluate the effect of terfenadine against Entamoeba histolytica. The trophozoites were exposed to 1, 2, 3, and 4 μM of terfenadine, for 24 and 48 h. Consequently, the viability of cells was determined by trypan blue exclusion test. The effect of terfenadine on adhesion of Entamoeba histolytica was evaluated in Caco-2 cells. In addition, the effect of terfenadine on the erythrophagocytic capacity of the parasite was investigated. The results show that terfenadine affects the growth and cell viability in a time- and dose-dependent manner. The higher inhibitory effects were observed with 4 µM at 48 h; 91.6% of growth inhibition and only 22.5% of trophozoites were viable. Additionally, we demonstrate that terfenadine is highly selective for the parasite and has low toxicity on Caco-2 cells. Furthermore, adhesion to Caco-2 cells and erythrophagocytic capacity were significantly inhibited. These findings demonstrate that terfenadine exerts significant effects on the virulence of Entamoeba histolytica. This is the first study demonstrating the amoebicidal activity of terfenadine and the results suggest it may be effective in the treatment of amoebiasis.
- Published
- 2021
47. Acquired (Drug-Induced) Long and Short QT Syndromes
- Author
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Shah, Rashmi R., Gussak, Ihor, Gussak, Ihor, editor, and Antzelevitch, Charles, editor
- Published
- 2013
- Full Text
- View/download PDF
48. Different voltage dependence of ICaL blockade in nonselective IKr blockers causes their opposite effects on early afterdepolarization in drug-induced arrhythmia
- Author
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Shingo Murakami and Akira Kimura
- Subjects
0301 basic medicine ,Pharmacology ,Chemistry ,RM1-950 ,Computer simulation ,Drug induced arrhythmia ,Amiodarone ,Blockade ,Afterdepolarization ,Drug-induced arrhythmia ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Delayed rectifier ,Bepridil ,medicine ,Molecular Medicine ,Voltage dependence ,Terfenadine ,ICaL ,Therapeutics. Pharmacology ,Early afterdepolarization ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Several false-positive results in the human ether-a-gogo-related gene test suggest that blockers of the rapid component of delayed rectifier K+ current (IKr) do not necessarily produce drug-induced arrhythmias. Specifically, the occurrence of early afterdepolarization (EAD) differs among IKr blockers, even if the prolonged action potential duration is in the same range. To predict EAD in drug-induced arrhythmias, we proposed a prediction method based on the mechanisms underlying the difference in frequency of EAD among nonselective IKr blockers. The mechanisms were elucidated by examining how different blockade kinetics of L-type Ca2+ current (ICaL) affect the frequency of EAD, using mathematical models of human ventricular myocytes. Addition of voltage-independent ICaL blockade resulted in the suppression of EAD. However, when voltage-dependent ICaL blockade kinetics of amiodarone, bepridil, and terfenadine were incorporated into ICaL in the model, bepridil and terfenadine induced EAD more than the voltage-independent ICaL blockade, while amiodarone suppressed EAD more effectively. Opposite effects were accounted for by the difference in ICaL blockade at negatively polarized potential. EAD occurrence was found to be associated with ICaL blockade measured at -20 mV. These results suggest that voltage dependence of ICaL blockade may be useful in predicting the different risks of nonselective IKr blockers.
- Published
- 2021
49. Torsade de pointes associated with long-term antiretroviral drugs in a patient with HIV: a case report.
- Author
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Mu X, Duan Y, Xu Q, Wang S, Gao G, Han N, and Zhao H
- Abstract
With the improving life expectancy of patients with human immunodeficiency virus (HIV), there is an increasing health concern of potential toxicity and drug interactions of long-term antiretroviral therapies. We describe a female patient with HIV, who was admitted to the emergency department following an unexplained loss of consciousness. This patient had been on antiretroviral therapy comprising tenofovir disoproxil fumarate, lamivudine, and lopinavir/ritonavir for 12 years. Coincidentally, she had been prescribed terfenadine for urticaria recently. After 3 days on this medication, she suddenly lost her consciousness, with a distinctive electrocardiogram alteration characterized by QT prolongation and torsade de pointes. This symptom recurred several times over a span of 2 days. We postulate that the primary instigator was an elevated concentration of terfenadine, which can be traced back to her antiretroviral therapy regimen comprising lopinavir/ritonavir. This drug is known to impede the metabolism of cytochrome P450 3A4 substrates and consequently elevate terfenadine concentrations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mu, Duan, Xu, Wang, Gao, Han and Zhao.)
- Published
- 2023
- Full Text
- View/download PDF
50. Cardiac Disease Alters Myocardial Tissue Levels of Epoxyeicosatrienoic Acids and Key Proteins Involved in Their Biosynthesis and Degradation
- Author
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Theresa Aliwarga, Jean C. Dinh, Scott Heyward, Bhagwat Prasad, Sina A. Gharib, Rozenn N. Lemaitre, Nona Sotoodehnia, and Rheem A. Totah
- Subjects
Epoxide Hydrolases ,Arachidonic Acid ,Heart Diseases ,Organic Chemistry ,General Medicine ,Cytochrome P-450 CYP2J2 ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,EETs ,cis-EET ,trans-EET ,CYP2J2 ,Cytochrome P450 ,POR ,EPHX2 ,CVD ,arachidonic acid ,proteomics ,cardiac tissue ,Cytochrome P-450 Enzyme System ,Cardiovascular Diseases ,Humans ,Eicosanoids ,Terfenadine ,Physical and Theoretical Chemistry ,Molecular Biology ,NADP ,Spectroscopy - Abstract
CYP2J2 is the main epoxygenase in the heart that is responsible for oxidizing arachidonic acid to cis-epoxyeicosatrienoic acids (EETs). Once formed, EETs can then be hydrolyzed by soluble epoxide hydrolase (sEH, encoded by EPHX2) or re-esterified back to the membrane. EETs have several cardioprotective properties and higher levels are usually associated with better cardiac outcomes/prognosis. This study investigates how cardiovascular disease (CVD) can influence total EET levels by altering protein expression and activity of enzymes involved in their biosynthesis and degradation. Diseased ventricular cardiac tissues were collected from patients receiving Left Ventricular Assist Device (LVAD) or heart transplants and compared to ventricular tissue from controls free of CVD. EETs, and enzymes involved in EETs biosynthesis and degradation, were measured using mass spectrometric assays. Terfenadine hydroxylation was used to probe CYP2J2 activity. Significantly higher cis- and trans-EET levels were observed in control cardiac tissue (n = 17) relative to diseased tissue (n = 24). Control cardiac tissue had higher CYP2J2 protein levels, which resulted in higher rate of terfenadine hydroxylation, compared to diseased cardiac tissues. In addition, levels of both NADPH-Cytochrome P450 oxidoreductase (POR) and sEH proteins were significantly higher in control versus diseased cardiac tissue. Overall, alterations in protein and activity of enzymes involved in the biosynthesis and degradation of EETs provide a mechanistic understanding for decreased EET levels in diseased tissues.
- Published
- 2022
- Full Text
- View/download PDF
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