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G. Bianchi Porro - One of the best experts on this subject based on the ideXlab platform.
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Double-blind, randomized trial of Roxatidine 150 mg in the early evening versus bedtime administration in the short-term treatment of duodenal ulcer
Alimentary pharmacology & therapeutics, 2007Co-Authors: M. Lazzaroni, A. Canali, G. Bianchi PorroAbstract:SUMMARY Aim: To compare the efficacy and tolerability of early evening (19.00–21.00 hours) vs. bedtime (22.00–00.00 hours) oral administration of Roxatidine 150 mg in the short-term treatment of active duodenal ulcer. Methods: The trial was randomized, double-blind and double-dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to Roxatidine in the early evening (n= 139) or Roxatidine at bedtime (n= 137). Results: After 4 weeks, 78% of patients receiving Roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per-protocol analysis. With intention-to-treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84% (intention-to-treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer-related symptoms. Conclusions: This study confirmed the healing and analgesic properties of Roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with Roxatidine 150 mg resulted in similar 4- to 8-week rates of duodenal ulcer healing.
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Twenty-four-hour intragastric acidity following early evening or bedtime administration of Roxatidine in duodenal ulcer patients.
Alimentary pharmacology & therapeutics, 1996Co-Authors: M. Lazzaroni, O. Sangaletti, S. Bargiggia, G. Bensi, A. Canali, G. Bianchi PorroAbstract:Aim: To assess the usefulness of early evening administration of Roxatidine 150 mg as an alternative to the traditional bedtime regimen. Methods: Twenty-four patients with healed duodenal ulcer were dosed according to a balanced incomplete-block design, with two of the following regimens: placebo, Roxatidine 150 mg at 07.30 h (early evening) or Roxatidine 150 mg at 22.00 h (bedtime). Twenty-four-hour intragastric pH-metry was started at 18.00 h on the first day of dosing. Median pH was determined for the 24-h period, and for the following time intervals: 20.00–00.00 h, 00.00–08.00 h and 08.00–18.00 h. Percentage time in the 24-h period with pH greater than 4.0 was also calculated. Results: The two Roxatidine regimens proved significantly superior to the placebo, decreasing 24-h acidity for all the time intervals, except the 20.00–00.00 h period, when mean intragastric pH with the early evening regimen (4.5±1.1) proved significantly higher than after placebo (2.2±1.0) or when Roxatidine was taken at bedtime (2.4±1.1). Conclusion: Early evening administration of Roxatidine may afford satisfactory control of 24-h acidity, offering a useful alternative to conventional bedtime administration.
Susumu Okabe - One of the best experts on this subject based on the ideXlab platform.
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Roxatidine- and cimetidine-induced angiogenesis inhibition suppresses growth of colon cancer implants in syngeneic mice.
Journal of pharmacological sciences, 2003Co-Authors: Kazuyoshi Tomita, Kazuki Izumi, Susumu OkabeAbstract:ABSTRACT Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H2-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of Roxatidine acetate hydrochloride (Roxatidine), an H2-receptor antagonist, on the growth of colon cancer implanted in mice was examined and compared with that of cimetidine. Drugs were orally delivered for 26 – 29 days beginning before or after implantation of syngeneic colon cancer (Colon 38) in C57BL/6 mice. Tumor volume was determined throughout and histochemical analysis was also performed. Tumor tissue and serum vascular endothelial growth factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT assay. Both Roxatidine and cimetidine significantly suppressed the growth of Colon 38 tumor implants. Histologic analysis revealed that such antagonists markedly increased necrotic areas and decreased the density of microvessels in tumor tissue. Both H2-receptor antagonists suppressed VEGF levels in tumor tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice. Such drugs, however, failed to suppress in vitro growth of the cell line. In conclusion, both Roxatidine and cimetidine were found to exert suppressive effects on the growth of colon cancer implants in mice by inhibiting angiogenesis via reducing VEGF expression.
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Roles of Extracellular Ca++ and Calmodulin in Roxatidine-Stimulated Secretion and Synthesis of Mucus by Cultured Rabbit Gastric Mucosal Cells
The Journal of pharmacology and experimental therapeutics, 1998Co-Authors: Satoru Takahashi, Susumu OkabeAbstract:We found that Roxatidine stimulates mucus secretion and synthesis by cultured rabbit gastric mucosal cells. In this study, we examined the roles of the extracellular Ca++ and calmodulin in these effects of Roxatidine. Reduction of the extracellular Ca++concentration decreased the Roxatidine-induced increases in mucus secretion and synthesis by gastric mucosal cells. Roxatidine concentration-dependently promoted Ca++ influx and caused an increase in intracellular Ca++. After the addition of Roxatidine, the increases in the secretion and synthesis reflected those in Ca++ influx and intracellular Ca++concentration and then disappeared as Ca++ influx and intracellular Ca++ concentration returned to the control level. The Roxatidine-stimulated Ca++ influx and intracellular Ca++ mobilization were abolished by reduction of the extracellular Ca++ concentration. Nifedipine and diltiazem inhibited both the effects of Roxatidine, but even at 10 μM, the inhibition was partial. Furthermore, W-7 (a calmodulin antagonist) completely abolished the effects of Roxatidine on mucus secretion and synthesis without causing a reduction of the stimulated Ca++ influx. Taken together, these results suggest that Roxatidine promotes Ca++ influx through both voltage-sensitive Ca++ channels and other Ca++entry gates and the subsequent intracellular Ca++mobilization, leading to potentiation of mucus secretion and synthesis by rabbit gastric mucosal cells. In addition, Ca++-activated calmodulin may play a pivotal role in these stimulatory effects of Roxatidine.
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roles of extracellular ca and calmodulin in Roxatidine stimulated secretion and synthesis of mucus by cultured rabbit gastric mucosal cells
Journal of Pharmacology and Experimental Therapeutics, 1998Co-Authors: Satoru Takahashi, Susumu OkabeAbstract:We found that Roxatidine stimulates mucus secretion and synthesis by cultured rabbit gastric mucosal cells. In this study, we examined the roles of the extracellular Ca++ and calmodulin in these effects of Roxatidine. Reduction of the extracellular Ca++concentration decreased the Roxatidine-induced increases in mucus secretion and synthesis by gastric mucosal cells. Roxatidine concentration-dependently promoted Ca++ influx and caused an increase in intracellular Ca++. After the addition of Roxatidine, the increases in the secretion and synthesis reflected those in Ca++ influx and intracellular Ca++concentration and then disappeared as Ca++ influx and intracellular Ca++ concentration returned to the control level. The Roxatidine-stimulated Ca++ influx and intracellular Ca++ mobilization were abolished by reduction of the extracellular Ca++ concentration. Nifedipine and diltiazem inhibited both the effects of Roxatidine, but even at 10 μM, the inhibition was partial. Furthermore, W-7 (a calmodulin antagonist) completely abolished the effects of Roxatidine on mucus secretion and synthesis without causing a reduction of the stimulated Ca++ influx. Taken together, these results suggest that Roxatidine promotes Ca++ influx through both voltage-sensitive Ca++ channels and other Ca++entry gates and the subsequent intracellular Ca++mobilization, leading to potentiation of mucus secretion and synthesis by rabbit gastric mucosal cells. In addition, Ca++-activated calmodulin may play a pivotal role in these stimulatory effects of Roxatidine.
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Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with Roxatidine.
Japanese journal of pharmacology, 1992Co-Authors: Susumu Okabe, Keiko Takagi, Hideki Igata, Shinichi Kato, Kenichi Shimosako, Yoshiaki Yamaji, Masao SeikiAbstract:We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (Roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and Roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with Roxatidine. Z-300, but not Roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.
M. Lazzaroni - One of the best experts on this subject based on the ideXlab platform.
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Double-blind, randomized trial of Roxatidine 150 mg in the early evening versus bedtime administration in the short-term treatment of duodenal ulcer
Alimentary pharmacology & therapeutics, 2007Co-Authors: M. Lazzaroni, A. Canali, G. Bianchi PorroAbstract:SUMMARY Aim: To compare the efficacy and tolerability of early evening (19.00–21.00 hours) vs. bedtime (22.00–00.00 hours) oral administration of Roxatidine 150 mg in the short-term treatment of active duodenal ulcer. Methods: The trial was randomized, double-blind and double-dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to Roxatidine in the early evening (n= 139) or Roxatidine at bedtime (n= 137). Results: After 4 weeks, 78% of patients receiving Roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per-protocol analysis. With intention-to-treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84% (intention-to-treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer-related symptoms. Conclusions: This study confirmed the healing and analgesic properties of Roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with Roxatidine 150 mg resulted in similar 4- to 8-week rates of duodenal ulcer healing.
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Twenty-four-hour intragastric acidity following early evening or bedtime administration of Roxatidine in duodenal ulcer patients.
Alimentary pharmacology & therapeutics, 1996Co-Authors: M. Lazzaroni, O. Sangaletti, S. Bargiggia, G. Bensi, A. Canali, G. Bianchi PorroAbstract:Aim: To assess the usefulness of early evening administration of Roxatidine 150 mg as an alternative to the traditional bedtime regimen. Methods: Twenty-four patients with healed duodenal ulcer were dosed according to a balanced incomplete-block design, with two of the following regimens: placebo, Roxatidine 150 mg at 07.30 h (early evening) or Roxatidine 150 mg at 22.00 h (bedtime). Twenty-four-hour intragastric pH-metry was started at 18.00 h on the first day of dosing. Median pH was determined for the 24-h period, and for the following time intervals: 20.00–00.00 h, 00.00–08.00 h and 08.00–18.00 h. Percentage time in the 24-h period with pH greater than 4.0 was also calculated. Results: The two Roxatidine regimens proved significantly superior to the placebo, decreasing 24-h acidity for all the time intervals, except the 20.00–00.00 h period, when mean intragastric pH with the early evening regimen (4.5±1.1) proved significantly higher than after placebo (2.2±1.0) or when Roxatidine was taken at bedtime (2.4±1.1). Conclusion: Early evening administration of Roxatidine may afford satisfactory control of 24-h acidity, offering a useful alternative to conventional bedtime administration.
Kyung-tae Lee - One of the best experts on this subject based on the ideXlab platform.
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Roxatidine attenuates mast cell-mediated allergic inflammation via inhibition of NF-κB and p38 MAPK activation.
Scientific reports, 2017Co-Authors: Minho Lee, Na Young Lee, Kyung-sook Chung, Se-yun Cheon, Kyung-tae LeeAbstract:Roxatidine is an active metabolite of Roxatidine acetate hydrochloride which is a histamine H2-receptor antagonist that is used to treat gastric and duodenal ulcers. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of Roxatidine in phorbol 12-myristate 13-acetate and calcium ionophore (PMACI)-stimulated human mast cells-1 (HMC-1), compound 48/80-induced anaphylactic animal model and chemical allergen-induced contact hypersensitivity (CHS) models. Roxatidine suppressed the mRNA and protein expression of inflammatory cytokines such as TNF-α, IL-6, and IL-1β in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In addition, Roxatidine attenuated PMACI-induced nuclear translocation of NF-κB and the phosphorylation of MKK3/6 and MK2, which are both involved in the p38 MAPK pathway. Furthermore, we observed that Roxatidine suppressed the activation of caspase-1, an IL-1β converting enzyme, in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In CHS model, Roxatidine significantly reduced ear swelling, increased number of mast cells, production levels of cytokines and migration of dendritic cells. Our findings provide evidence that the anti-allergic inflammatory properties of Roxatidine are mediated by the inhibition of NF-κB and caspase-1 activation, p38 MAPK pathway and mast cell-derived cytokine production. Taken together, the in vitro and in vivo anti-allergic inflammatory effects suggest a possible therapeutic application of Roxatidine in allergic inflammatory diseases.
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Roxatidine suppresses inflammatory responses via inhibition of nf κb and p38 mapk activation in lps induced raw 264 7 macrophages
Journal of Cellular Biochemistry, 2011Co-Authors: Eu-jin Cho, Ji-sun Shin, Hye-eun Choi, Young-wuk Cho, Hyung-min Kim, Jung-hye Choi, Kyung-tae LeeAbstract:Roxatidine is a novel, specific, competitive H(2) -receptor antagonist that is used to treat gastric and duodenal ulcers, and which is known to suppress the growth of several tumors by reducing vascular endothelial growth factor (VEGF) expression. Nevertheless, it remains unclear whether Roxatidine has anti-inflammatory effects. In this study, we the authors investigated the anti-inflammatory effect of Roxatidine in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. It was found that Roxatidine dose-dependently inhibited the productions of prostaglandin E(2) (PGE(2)), nitric oxide (NO), and histamine, and the protein and mRNA expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and histidine decarboxylase (HDC). In addition, Roxatidine reduced the productions and expressions of VEGF-1 and pro-inflammatory cytokines, including those of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Electrophoretic mobility shift assays (EMSA) and reporter gene assays revealed that treatment with Roxatidine attenuated the LPS-induced DNA-binding and transcriptional activity of nuclear factor kappa B (NF-κB). In addition, it was found that pretreatment with Roxatidine significantly inhibited the nuclear translocations of the p65 and p50 subunits of NF-κB, and these inhibitions were not found to be associated with decreases in the phosphorylation or degradation of inhibitory kappa B-α (IκBα). Furthermore, Roxatidine suppressed the phosphorylation of p38 MAP kinase, but not of IκB kinase-α/β (IKKα/β), c-Jun NH(2) -terminal kinase (JNK), or extracellular signal-regulated kinase (ERK). Taken together, these results indicate that the anti-inflammatory properties of Roxatidine in LPS-treated RAW 264.7 macrophages are mediated by the inhibition of NF-κB transcriptional activity and the p38 MAP kinase pathway.
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Roxatidine suppresses inflammatory responses via inhibition of NF‐κB and p38 MAPK activation in LPS‐induced RAW 264.7 macrophages
Journal of cellular biochemistry, 2011Co-Authors: Eu-jin Cho, Ji-sun Shin, Hye-eun Choi, Young-wuk Cho, Hyung-min Kim, Jung-hye Choi, Kyung-tae LeeAbstract:Roxatidine is a novel, specific, competitive H(2) -receptor antagonist that is used to treat gastric and duodenal ulcers, and which is known to suppress the growth of several tumors by reducing vascular endothelial growth factor (VEGF) expression. Nevertheless, it remains unclear whether Roxatidine has anti-inflammatory effects. In this study, we the authors investigated the anti-inflammatory effect of Roxatidine in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. It was found that Roxatidine dose-dependently inhibited the productions of prostaglandin E(2) (PGE(2)), nitric oxide (NO), and histamine, and the protein and mRNA expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and histidine decarboxylase (HDC). In addition, Roxatidine reduced the productions and expressions of VEGF-1 and pro-inflammatory cytokines, including those of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Electrophoretic mobility shift assays (EMSA) and reporter gene assays revealed that treatment with Roxatidine attenuated the LPS-induced DNA-binding and transcriptional activity of nuclear factor kappa B (NF-κB). In addition, it was found that pretreatment with Roxatidine significantly inhibited the nuclear translocations of the p65 and p50 subunits of NF-κB, and these inhibitions were not found to be associated with decreases in the phosphorylation or degradation of inhibitory kappa B-α (IκBα). Furthermore, Roxatidine suppressed the phosphorylation of p38 MAP kinase, but not of IκB kinase-α/β (IKKα/β), c-Jun NH(2) -terminal kinase (JNK), or extracellular signal-regulated kinase (ERK). Taken together, these results indicate that the anti-inflammatory properties of Roxatidine in LPS-treated RAW 264.7 macrophages are mediated by the inhibition of NF-κB transcriptional activity and the p38 MAP kinase pathway.
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Quantification of Roxatidine in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry: application to a bioequivalence study.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2008Co-Authors: Ju-hee Ryu, Sang-jun Choi, Heon-woo Lee, Seung-ki Choi, Kyung-tae LeeAbstract:Abstract A sensitive and specific method using a one-step liquid–liquid extraction (LLE) with ethyl acetate followed by high-performance liquid chromatography (HPLC) coupled with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection was developed and validated for the determination of Roxatidine in human plasma using famotidine as an internal standard (IS). Data acquisition was carried out in multiple reaction monitoring (MRM) mode, by monitoring the transitions m / z 307.3 → 107.1 for Roxatidine and m / z 338.4 → 189.1 for famotidine. Chromatographic separation was performed on a reverse phase Hydrosphere C 18 column at 0.2 mL min −1 using a mixture of methanol–ammonium formate buffer as mobile phase (20:80, v/v; adjusted to pH 3.9 with formic acid). The achieved lower limit of quantification (LLOQ) was 1.0 ng mL −1 and the standard calibration curve for Roxatidine was linear ( r 2 = 0.998) over the studied range (1–1000 ng mL −1 ) with acceptable accuracy and precision. Roxatidine was found to be stable in human plasma samples under short-, long-term storage and processing conditions. The developed method was validated and successfully applied to the bioequivalence study of Roxatidine administrated as a single oral dose (75 mg as Roxatidine acetate hydrochloride) to healthy female Korean volunteers.
U Klotz - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and pharmacodynamics of Roxatidine in patients with renal insufficiency.
British journal of clinical pharmacology, 1995Co-Authors: U. Gladziwa, S Wagner, H. G. Sieberth, U KlotzAbstract:1. Roxatidine acetate, a new histamine H2-receptor antagonist, was administered in the evening (75 mg p.o.) to eight patients with renal insufficiency (CLCR 8-17 ml min-1) for 12 days and plasma drug concentrations were measured. 2. Ambulatory intragastric pH was monitored following the last dose and values were compared with those on day 1 when all patients received a placebo. 3. The terminal elimination half-life (mean +/- s.d.) of Roxatidine was 10.8 +/- 2.4 h and its oral clearance was 178 +/- 43 ml min-1. 4. During Roxatidine treatment gastrin levels increased slightly (median 189 vs 289 ng l-1) and the hyperparathyroid status of the patients was almost normalized (parathyroid hormone levels: median 199 vs 132 ng l-1). 5. The mean latency to a gastric pH of at least 4 was 4.3 +/- 1.4 h. The duration of action (intragastric pH > 4) was 10.6 +/- 3.9 h. 6. As in a pilot study with six patients (CLCR 4 for more than 6 h, daily nocturnal intake of 75 mg Roxatidine acetate appears appropriate to elevate gastric pH > 4 for a sufficient period of time.
