The Experts below are selected from a list of 3546 Experts worldwide ranked by ideXlab platform
Genichiro Soma - One of the best experts on this subject based on the ideXlab platform.
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oral Administration of pantoea agglomerans derived lipopolysaccharide prevents development of atherosclerosis in high fat diet fed apoe deficient mice via ameliorating hyperlipidemia pro inflammatory mediators and oxidative responses
PLOS ONE, 2018Co-Authors: Yutaro Kobayashi, Hiroyuki Inagawa, Chie Kohchi, Kimiko Kazumura, Hiroshi Tsuchiya, Toshiyuki Miwa, Katsuichiro Okazaki, Genichiro SomaAbstract:Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or Sublingual Administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral Administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.
Hiroyuki Inagawa - One of the best experts on this subject based on the ideXlab platform.
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oral Administration of pantoea agglomerans derived lipopolysaccharide prevents development of atherosclerosis in high fat diet fed apoe deficient mice via ameliorating hyperlipidemia pro inflammatory mediators and oxidative responses
PLOS ONE, 2018Co-Authors: Yutaro Kobayashi, Hiroyuki Inagawa, Chie Kohchi, Kimiko Kazumura, Hiroshi Tsuchiya, Toshiyuki Miwa, Katsuichiro Okazaki, Genichiro SomaAbstract:Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or Sublingual Administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral Administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.
Pierre A.m. Peeters - One of the best experts on this subject based on the ideXlab platform.
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the effect of food on the high clearance drug asenapine after Sublingual Administration to healthy male volunteers
European Journal of Clinical Pharmacology, 2015Co-Authors: Peter Dogterom, Rik Greef, Pierre A.m. PeetersAbstract:PURPOSE: To determine the effects of food on the pharmacokinetics of Sublingual asenapine. METHODS: Healthy male volunteers (n=26, age 19-53 years) randomly received a single Sublingual dose of asenapine 5 mg after ≥ 10 h fasting (Treatment A, reference), after a high-fat meal (Treatment B) and after ≥ 10 h fasting with a high-fat meal at 4 h post-dose (Treatment C). Blood samples were drawn over 72 h to measure asenapine plasma concentrations. Effects of food intake on asenapine pharmacokinetics were assessed using bioequivalence criteria and evaluated using a compartmental modelling analysis. RESULTS: Compared with the reference, mean asenapine exposure (AUC0-last and AUC0-∞) was approximately 20 % lower after intake of a high-fat meal prior to dosing, whereas Cmax decreased by only about 10 %. When a high-fat meal was taken 4 h post-dose in the fasting state, asenapine concentrations were similar to the reference during the first 4 h post-dose. After the meal intake, asenapine concentrations decreased quickly for several hours. Compartmental modelling indicated that a transient 2.5-fold increase in asenapine clearance after eating could explain the asenapine concentration-time profiles for both food regimens. CONCLUSIONS: To our knowledge, this is the first study investigating the effect of food upon the Sublingual Administration of a drug. A high-fat meal taken before or 4 h post-dose of Sublingual asenapine indirectly caused a transient increase in liver blood flow that resulted in a temporal increase in asenapine clearance. As the effects on asenapine exposure were small and not clinically relevant, no additional restrictions are required for the timing of food intake in relation to asenapine dosing.
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effect of absorption site on the pharmacokinetics of Sublingual asenapine in healthy male subjects
Biopharmaceutics & Drug Disposition, 2010Co-Authors: Mireille Gerrits, Rik Greef, Pierre A.m. PeetersAbstract:Asenapine is a psychopharmacologic agent approved in the United States for the acute treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. It is pending approval for the treatment of schizophrenia and manic episodes associated with bipolar I disorder in Europe. Asenapine is administered as a Sublingual formulation. To determine whether the pharmacokinetics of asenapine are impacted by placing the tablet buccally ('cheeking') or allowing the tablet to dissolve on the top of the tongue, pharmacokinetics were compared following buccal and supralingual Administration versus Sublingual Administration. In this open-label, randomized, 3-way crossover trial, healthy men (n=36) received single 5 mg doses of asenapine via Sublingual, supralingual and buccal routes, at least 1 week apart. With buccal Administration, the area under the concentration-over-time curve (AUC(0-infinity)) and peak concentration (C(max)) were, respectively, 24%, and 19% higher than with Sublingual Administration; these routes were not bioequivalent. With supralingual Administration, AUC(0-infinity) and C(max) were 6% and 13% lower than with Sublingual Administration; bioequivalence was established based on AUC(0-infinity) only; bioequivalence based on C(max) could not be assessed due to 40% within-subject variability. The most common adverse events were oral paresthesia (Sublingual, 75.8%; supralingual, 55.9%; buccal, 45.7%) and somnolence (81.8%; 76.5%; 68.6%). Compared with the recommended Sublingual route of asenapine Administration, exposure was 24% higher with buccal Administration and comparable to supralingual Administration. However, differences in exposure associated with variable placement in the oral cavity did not compromise safety in healthy subjects.
Yutaro Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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oral Administration of pantoea agglomerans derived lipopolysaccharide prevents development of atherosclerosis in high fat diet fed apoe deficient mice via ameliorating hyperlipidemia pro inflammatory mediators and oxidative responses
PLOS ONE, 2018Co-Authors: Yutaro Kobayashi, Hiroyuki Inagawa, Chie Kohchi, Kimiko Kazumura, Hiroshi Tsuchiya, Toshiyuki Miwa, Katsuichiro Okazaki, Genichiro SomaAbstract:Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or Sublingual Administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral Administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.
Carlo Foresta - One of the best experts on this subject based on the ideXlab platform.
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Sublingual Administration of sildenafil oro dispersible film new profiles of drug tolerability and pharmacokinetics for pde5 inhibitors
Frontiers in Pharmacology, 2018Co-Authors: Luca De Toni, Maurizio De Rocco Ponce, Erica Franceschinis, Stefano Dallacqua, Roberto Padrini, Nicola Realdon, Andrea Garolla, Carlo ForestaAbstract:Objective. Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the Sublingual Administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film coated tablet (FCT) as original per os formulation. Methods. In vitro disaggregation test, dissolution test and permeation test in specific devices to estimate the trans-mucosal absorption. In vivo analysis of serum Sild levels, by HPLC-MS/MS, was performed in 20 patients with psychogenic ED receiving alternatively per os FCT or Sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and adverse drug reactions experienced after the dosing of each formulation were compared. Results. In vitro, ODF showed the highest time to disaggregation and an increased rate of permeation compared to both ODT and FCT (P=0,017 and P=0,008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster increase of serum Sild levels (serum levels at 15 min from dosing respectively: 2,24±1,4 ng/mL FCT, 0,5±0,3 ng/mL ODT and 13,5±9,1 ng/mL ODF; P<0,01 and P<0,05 vs ODF) together with a higher drug bioavailability within 60 minutes from dosing (relative AUC60min vs FCT respectively: 100,0±44,9% FCT, 183,8±75,4% ODT and 304,2±156,0% ODF). A trend towards lower peak serum levels was observed for ODF. Finally, ODF showed a lower prevalence of headache compared to FCT (1% vs 35%; P<0,05) and improved pattern of flushing and nasal congestion. Conclusion. Sublingual Sild oro-dispersible film improves the drug tolerability through a likely modified pharmacokinetic, suggesting a possible implication also in the clinical efficacy profile. Sublingual Administration of oro-dispersible formulations may represent a strategy to ameliorate the adherence to therapy with PDE5i, particularly in patients discouraged by side effects.
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Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors
Frontiers Media S.A., 2018Co-Authors: Luca De Toni, Maurizio De Rocco Ponce, Erica Franceschinis, Roberto Padrini, Nicola Realdon, Andrea Garolla, Stefano Dall’acqua, Carlo ForestaAbstract:Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the Sublingual Administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film-coated tablet (FCT) as original per os formulation.Methods:In vitro disaggregation test, dissolution test, and permeation test in specific devices to estimate the trans-mucosal absorption. In vivo analysis of serum Sild levels, by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), was performed in 20 patients with psychogenic ED receiving alternatively per os FCT or Sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and adverse drug reactions experienced after the dosing of each formulation were compared.Results:In vitro, ODF showed the highest time to disaggregation and an increased rate of permeation compared to both ODT and FCT (P = 0.017 and P = 0.008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster increase of serum Sild levels (serum levels at 15 min from dosing, respectively: 2.24 ± 1.4 ng/ml FCT, 0.5 ± 0.3 ng/ml ODT, and 13.5 ± 9.1 ng/ml ODF; P < 0.01 and P < 0.05 vs. ODF) together with a higher drug bioavailability within 60 min from dosing (relative AUC60min vs. FCT, respectively: 100.0 ± 44.9% FCT, 183.8 ± 75.4% ODT, and 304.2 ± 156.0% ODF). A trend toward lower peak serum levels was observed for ODF. Finally, ODF showed a lower prevalence of headache compared to FCT (1 vs. 35%; P < 0.05) and improved pattern of flushing and nasal congestion.Conclusion: Sublingual Sild ODF improves the drug tolerability through a likely modified pharmacokinetic, suggesting a possible implication also in the clinical efficacy profile. Sublingual Administration of oro-dispersible formulations may represent a strategy to ameliorate the adherence to therapy with PDE5i, particularly in patients discouraged by side effects
