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Hiroyuki Itoh - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective properties of Pirfenidone in subtotally nephrectomized rats.
European journal of pharmacology, 2009Co-Authors: Koji Takakuta, Akira Fujimori, Toshihiro Chikanishi, Akira Tanokura, Yoshiyuki Iwatsuki, Masanori Yamamoto, Hidenori Nakajima, Masamichi Okada, Hiroyuki ItohAbstract:Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of Pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing Pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, Pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, Pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, Pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that Pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although Pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation.
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Renoprotective properties of Pirfenidone in subtotally nephrectomized rats
European Journal of Pharmacology, 2009Co-Authors: Koji Takakuta, Akira Fujimori, Toshihiro Chikanishi, Akira Tanokura, Yoshiyuki Iwatsuki, Masanori Yamamoto, Hidenori Nakajima, Masamichi Okada, Hiroyuki ItohAbstract:Abstract Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of Pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing Pirfenidone (approximately 700 mg/kg/day) for 8 weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, Pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, Pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-β and fibronectin in the mRNA of the kidney. In contrast, Pirfenidone had little effect on the expression of α-smooth muscle actin, which is one of the proteins responsible for epithelial–mesenchymal transition. This property was confirmed by the TGF-β-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that Pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although Pirfenidone has less effective TGF-β-induced epithelial to mesenchymal transdifferentiation.
Rajat Walia - One of the best experts on this subject based on the ideXlab platform.
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Effect of Pirfenidone on wound healing in lung transplant patients
Multidisciplinary Respiratory Medicine, 2019Co-Authors: Amber Mortensen, Lauren Cherrier, Rajat WaliaAbstract:Background: The drug Pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking Pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether Pirfenidone should be discontinued prior to listing to allow for a wash-out period. Methods: We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. Results: We describe 18 patients who took Pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on Pirfenidone for at least 30 days; nine patients had been on Pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. Conclusions: In our experience, Pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when Pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with Pirfenidone before lung transplantation.
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Effect of Pirfenidone on wound healing in lung transplant patients.
Multidisciplinary respiratory medicine, 2018Co-Authors: Amber Mortensen, Lauren Cherrier, Rajat WaliaAbstract:The drug Pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking Pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether Pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took Pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on Pirfenidone for at least 30 days; nine patients had been on Pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, Pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when Pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with Pirfenidone before lung transplantation.
Koji Takakuta - One of the best experts on this subject based on the ideXlab platform.
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Renoprotective properties of Pirfenidone in subtotally nephrectomized rats.
European journal of pharmacology, 2009Co-Authors: Koji Takakuta, Akira Fujimori, Toshihiro Chikanishi, Akira Tanokura, Yoshiyuki Iwatsuki, Masanori Yamamoto, Hidenori Nakajima, Masamichi Okada, Hiroyuki ItohAbstract:Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of Pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing Pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, Pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, Pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, Pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that Pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although Pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation.
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Renoprotective properties of Pirfenidone in subtotally nephrectomized rats
European Journal of Pharmacology, 2009Co-Authors: Koji Takakuta, Akira Fujimori, Toshihiro Chikanishi, Akira Tanokura, Yoshiyuki Iwatsuki, Masanori Yamamoto, Hidenori Nakajima, Masamichi Okada, Hiroyuki ItohAbstract:Abstract Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of Pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing Pirfenidone (approximately 700 mg/kg/day) for 8 weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, Pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, Pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-β and fibronectin in the mRNA of the kidney. In contrast, Pirfenidone had little effect on the expression of α-smooth muscle actin, which is one of the proteins responsible for epithelial–mesenchymal transition. This property was confirmed by the TGF-β-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that Pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although Pirfenidone has less effective TGF-β-induced epithelial to mesenchymal transdifferentiation.
Takashi Ogura - One of the best experts on this subject based on the ideXlab platform.
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clinical experience of the long term use of Pirfenidone for idiopathic pulmonary fibrosis
Internal Medicine, 2016Co-Authors: Masashi Bando, Hiroyoshi Yamauchi, Takashi Ogura, Hiroyuki Taniguchi, Kentaro Watanabe, Arata Azuma, Sakae Homma, Yukihiko SugiyamaAbstract:Objective Long-term effects of Pirfenidone have been poorly understood to date. This study investigated the clinical efficacy and safety of long-term Pirfenidone use for idiopathic pulmonary fibrosis (IPF) in clinical practice. Methods This survey study was a retrospective observational study. A survey was used to collect clinical information on IPF cases that were treated with Pirfenidone. This survey sheet came from physicians belonging to the Diffuse Lung Diseases Research Group. Results 502 patients at 22 institutes received pirfeidone treatment. Of the 502 cases, Pirfenidone treatment was terminated in under one year in 186 cases (37.1%); adverse effect was the most frequent reason for termination. The Pirfenidone treatment lasted for two years or longer in 111 cases (22.1%). The mean change in the forced vital capacity (FVC) was -30±224 (SD) mL in the first year of treatment, -158±258 mL in the second year, and -201±367 mL in the third year. FVC improved by 10% or more in the first year in 10 (14.7%) of 68 cases, and showed a change of ±10% in 47 (69.1%) cases. It showed a change of ±10% in the second and third years in 61.7% and 62.5% of the patients, respectively. Conclusion The FVC improved in only a small percentage of patients who received Pirfenidone treatment for a long period of time. However, a decrease in the FVC was prevented for three years in over half of the cases.
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Safety and pharmacokinetics of nintedanib and Pirfenidone in idiopathic pulmonary fibrosis
The European respiratory journal, 2014Co-Authors: Takashi Ogura, Masashi Bando, Hiroyuki Taniguchi, Arata Azuma, Yasuhiro Kondoh, Yoshikazu Inoue, Yoshinori Hasegawa, Shinji Abe, Yoshiro Mochizuki, Kingo ChidaAbstract:A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing Pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving Pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to Pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to Pirfenidone. Nintedanib had no effect on the pharmacokinetics of Pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to Pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to Pirfenidone.
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Safety and efficacy of Pirfenidone in idiopathic pulmonary fibrosis in clinical practice.
Respiratory medicine, 2013Co-Authors: Ryo Okuda, Eri Hagiwara, Tomohisa Baba, Hideya Kitamura, Terufumi Kato, Takashi OguraAbstract:Summary Backgroud Previous Pirfenidone trials have only involved patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the safety and efficacy of Pirfenidone in patients with mild-to-severe IPF in clinical practice. Methods The clinical records of 76 patients who were diagnosed with IPF and received Pirfenidone were reviewed. Results The most frequent adverse event was anorexia, although the grade of anorexia in most patients was mild. Dose reduction of Pirfenidone improved anorexia in 84% affected patients, which resulted in a high medication compliance rate. The mean forced vital capacity (FVC) at the initiation of Pirfenidone therapy in this study was approximately 10% lower than that in previous clinical trials. The mean change in FVC during the 6-month period prior to the therapy initiation was −188 mL, which improved to −19 mL during the 6-month period after therapy. Significant attenuation in percentage predicted diffusion capacity of the lung for carbon monoxide decline was also achieved after Pirfenidone therapy initiation. The efficacy of Pirfenidone in attenuating the degree of FVC decline was higher in the group with FVC decline of ≥150 mL during the 6-month period prior to therapy initiation. The levels of serum markers, such as KL-6 and SP-D, were also lowered by the therapy. Conclusions These results showed that Pirfenidone was well-tolerated and had beneficial effects in patients with mild-to-severe and/or progressive IPF. The degree of disease progression prior to the initiation of Pirfenidone therapy had an impact on the response to the therapy.
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CT analysis of the effect of Pirfenidone in patients with idiopathic pulmonary fibrosis
European journal of radiology, 2012Co-Authors: Tae Iwasawa, Takashi Ogura, Tomohisa Baba, Fumikazu Sakai, Tetsu Kanauchi, Takanobu Komagata, Toshiyuki Gotoh, Satoshi Morita, Takuya Yazawa, Tomio InoueAbstract:Abstract Purpose Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to Pirfenidone therapy. Materials and methods Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with Pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs. Results The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the Pirfenidone group and 74.6 ± 16.6% in controls ( p = NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of Pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the Pirfenidone group than the control in both of visual score ( p = 0.006) and computer analysis ( p p Conclusion CT can be used to assess Pirfenidone-induced slowing of progression of pulmonary fibrosis.
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exploratory analysis of a phase iii trial of Pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment
Respiratory Research, 2011Co-Authors: Arata Azuma, Takashi Ogura, Hiroyuki Taniguchi, Yoshio Taguchi, Masahito Ebina, Yasuhiro Kondoh, Moritaka Suga, Hiroki Takahashi, Koichiro Nakata, Atsuhiko SatoAbstract:A phase III trial in Japan showed that Pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from Pirfenidone, we analyzed in an exploratory manner the data from the phase III trial. The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO2), and the lowest oxygen saturation by pulse oximetry (SpO2) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) Pirfenidone, low-dose (1200 mg/day) Pirfenidone, and placebo at week 52. Significant efficacy of Pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO2 < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, Pirfenidone significantly suppressed cough and dyspnea. IPF patients having %VC ≥ 70% and SpO2 < 90% at baseline will most likely benefit from Pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from Pirfenidone treatment. This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121).
Amber Mortensen - One of the best experts on this subject based on the ideXlab platform.
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Effect of Pirfenidone on wound healing in lung transplant patients
Multidisciplinary Respiratory Medicine, 2019Co-Authors: Amber Mortensen, Lauren Cherrier, Rajat WaliaAbstract:Background: The drug Pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking Pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether Pirfenidone should be discontinued prior to listing to allow for a wash-out period. Methods: We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. Results: We describe 18 patients who took Pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on Pirfenidone for at least 30 days; nine patients had been on Pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. Conclusions: In our experience, Pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when Pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with Pirfenidone before lung transplantation.
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Effect of Pirfenidone on wound healing in lung transplant patients.
Multidisciplinary respiratory medicine, 2018Co-Authors: Amber Mortensen, Lauren Cherrier, Rajat WaliaAbstract:The drug Pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking Pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether Pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took Pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on Pirfenidone for at least 30 days; nine patients had been on Pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, Pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when Pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with Pirfenidone before lung transplantation.