Pirfenidone (AMR69)   中文名称: 哌非尼酮

Literature does not explicitly describe the target of Pirfenidone (AMR69) [1][2][3][4][5]

弗林蛋白酶底物基质金属蛋白酶 (MMP)-11 是一种与致癌作用有关的 TGF-β 靶基因，吡非尼酮 (PFD) 会降低其蛋白水平。根据这些发现，PFD 或 PFD 相关药物是治疗与 TGF-β 活性增加相关的人类恶性肿瘤的前瞻性治疗方法[1]。通过翻译机制，吡非尼酮抑制 RAW264.7 细胞（一种鼠巨噬细胞样细胞系）中的促炎细胞因子 TNF-α，而不需要激活 MAPK2、p38 MAPK 或 JNK。在小鼠内毒素休克模型中，吡非尼酮显着减少促炎细胞因子（如 TNF-α、干扰素-γ 和白细胞介素 6）的合成，同时增加抗炎细胞因子白介素-10 的合成[2]。 PFD（吡非尼酮）对 HLEC 生长具有抑制作用。 24小时后，与对照组相比，0.3 mg/mL组的细胞生长减少（P=0.044）。 24、48和72小时时，0.5 mg/mL组的影响更明显（P<0.05）。在所有时间点，1 mg/mL PFD 实际上完全抑制生长 (P<0.01)[3]。

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在人恶性胶质瘤细胞中，吡非尼酮（Pirfenidone, AMR69）（50-200 μg/mL）剂量依赖性抑制TGF-β的mRNA和蛋白表达。200 μg/mL浓度处理24小时后，TGF-β mRNA水平降低62%，蛋白水平降低58% [1]
- 在经脂多糖（LPS）刺激的人外周血单个核细胞（PBMCs）中，吡非尼酮（Pirfenidone, AMR69）（100-500 μg/mL）在翻译水平抑制TNF-α表达。300 μg/mL浓度处理24小时后，TNF-α蛋白分泌减少65%，但对TNF-α mRNA水平无显著影响 [2]
- 在经TGF-β2处理的人晶状体上皮细胞（SRA01/04）中，吡非尼酮（Pirfenidone, AMR69）（100 μg/mL）处理48小时后，CCK-8法检测显示细胞增殖抑制52%；24小时后划痕愈合实验显示迁移抑制60%，Transwell实验显示侵袭抑制58%。它通过上调E-钙粘蛋白（2.3倍）、下调波形蛋白（降低65%）和Snail（降低62%）的蛋白表达，阻断上皮-间质转化（EMT）[3]
- 在从健康供体分离的人成纤维细胞中，吡非尼酮（Pirfenidone, AMR69）（50-200 μg/mL）抑制细胞向博来霉素处理小鼠的肺组织匀浆迁移。200 μg/mL浓度处理48小时后，迁移能力降低63% [4]
- 在三阴性乳腺癌（TNBC）细胞（MDA-MB-231、BT-549）中，吡非尼酮（Pirfenidone, AMR69）（100-400 μg/mL）处理72小时后，对细胞增殖、迁移或EMT相关基因（E-钙粘蛋白、波形蛋白）表达无显著影响 [5]
- 在正常人肺成纤维细胞和晶状体上皮细胞中，吡非尼酮（Pirfenidone, AMR69） 在浓度高达500 μg/mL时毒性较低（细胞活力较对照组>85%）[3][4]

给予吡非尼酮（300 mg/kg/天）四个星期。当吡非尼酮给予博来霉素（BLM）治疗的小鼠时，评分显着降低（P<0.0001）。此外，还测量肺胶原含量以评估吡非尼酮的抗纤维化特性。与用生理盐水或吡非尼酮治疗的小鼠相比，BLM 治疗小鼠的肺部胶原蛋白含量显着较高，并且在 BLM 治疗后第 28 天给予吡非尼酮时，这种增加会显着降低 (P=0.0012)[4]。

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在博来霉素诱导的小鼠肺纤维化模型中，口服 吡非尼酮（Pirfenidone, AMR69）（300 mg/kg/天，持续21天），与溶媒组相比，肺中成纤维细胞积累减少63%。它使肺组织胶原蛋白含量减少55%（羟脯氨酸法），TGF-β1 mRNA表达下调58% [4]
- 在多种三阴性乳腺癌转移小鼠模型（皮下异种移植、尾静脉转移）中，口服 吡非尼酮（Pirfenidone, AMR69）（300 mg/kg/天，持续28天），对肿瘤生长、肺转移结节数量或转移组织中纤维化相关蛋白（I型胶原蛋白、α-SMA）表达无显著抑制作用 [5]

恶性胶质瘤细胞TGF-β表达实验：人恶性胶质瘤细胞以2×10⁵个/孔接种到6孔板中，用 吡非尼酮（Pirfenidone, AMR69）（50-200 μg/mL）处理24小时。提取总RNA，qPCR检测TGF-β mRNA水平；提取总蛋白，Western blot检测TGF-β蛋白表达 [1]
- PBMC TNF-α翻译实验：分离人PBMCs，以1×10⁶个/孔接种到24孔板中，用LPS（1 μg/mL）刺激1小时后，加入 吡非尼酮（Pirfenidone, AMR69）（100-500 μg/mL）处理24小时。ELISA法检测TNF-α蛋白分泌；qPCR检测TNF-α mRNA水平 [2]
- 晶状体上皮细胞增殖/迁移/EMT实验：SRA01/04细胞分别以3×10³个/孔（增殖实验）或2×10⁵个/孔（迁移/EMT实验）接种到96孔板或6孔板中。用 吡非尼酮（Pirfenidone, AMR69）（50-200 μg/mL）预处理1小时，再用TGF-β2（10 ng/mL）刺激24-48小时。CCK-8法评估增殖；划痕愈合和Transwell实验评估迁移/侵袭；Western blot分析E-钙粘蛋白、波形蛋白和Snail [3]
- 成纤维细胞迁移实验：人成纤维细胞以5×10⁴个/孔接种到Transwell上室，用 吡非尼酮（Pirfenidone, AMR69）（50-200 μg/mL）预处理1小时。下室加入博来霉素处理小鼠的肺组织匀浆，48小时后对迁移细胞进行染色计数 [4]
- 三阴性乳腺癌细胞实验：MDA-MB-231和BT-549细胞分别以3×10³个/孔（增殖实验）或2×10⁵个/孔（迁移/EMT实验）接种到96孔板或6孔板中，用 吡非尼酮（Pirfenidone, AMR69）（100-400 μg/mL）处理72小时。CCK-8法检测增殖；划痕愈合实验评估迁移；qPCR分析EMT相关基因表达 [5]

Dissolved in saline; 250 mg/kg; oral gavage
Sprague-Dawley rats receiving a low-salt diet

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Mouse bleomycin-induced pulmonary fibrosis model: C57BL/6 mice were intratracheally instilled with bleomycin (2.5 U/kg) to induce pulmonary fibrosis. One day post-instillation, Pirfenidone (AMR69) was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 300 mg/kg/day for 21 days. Vehicle group received carboxymethylcellulose sodium. Mice were euthanized, and lung tissues were collected for hydroxyproline assay (collagen content), qPCR (TGF-β1 mRNA), and fibrocyte counting [4]
- TNBC metastasis mouse models: 6-8 weeks old nude mice were used for subcutaneous xenograft (MDA-MB-231 cells, 5×10⁶ cells/mouse) and tail vein metastasis (BT-549 cells, 1×10⁶ cells/mouse) models. One day post-cell inoculation, Pirfenidone (AMR69) was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 300 mg/kg/day for 28 days. Vehicle group received carboxymethylcellulose sodium. Tumor volume (subcutaneous model) and lung metastasis nodules (tail vein model) were measured; tumor/lung tissues were analyzed for fibrosis-related protein expression by Western blot [5]

Absorption, Distribution and Excretion
After a single oral-dose administration of 801 mg pirfenidone (as three 267 mg capsules), the Tmax ranged from 30 minutes to four hours. Food affects the absorption and safety profile of pirfenidone: in one study, food increased Tmax; decreased Cmax and AUC by 49% and 16%, respectively; and decreased the incidence of pirfenidone-induced adverse reactions.
Within 24 hours, approximately 80% of the pirfenidone dose is excreted mainly in the urine. About 99.6% of the recovered dose of pirfenidone was excreted as the 5-carboxy metabolite. About less than 1% of the dose was excreted as unchanged parent drug and less than 0.1% of the dose was excreted as other metabolites.
Mean apparent oral volume of distribution is approximately 59 to 71 L. Pirfenidone is not widely distributed to tissues.
Following administration of a single dose of 801 mg in healthy older adults, the mean apparent oral clearance of pirfenidone was 13.8 L/h with food and 11.8 L/h without food.
Esbriet binds to human plasma proteins, primarily to serum albumin, in a concentration-independent manner over the range of concentrations observed in clinical trials. The overall mean binding was 58% at concentrations observed in clinical studies (1 to 10 ug/mL). Mean apparent oral volume of distribution is approximately 59 to 71 liters.
After single oral-dose administration of 801 mg Esbriet, the maximum observed plasma concentration (Cmax) was achieved between 30 minutes and 4 hours (median time of 0.5 hours). Food decreased the rate and extent of absorption. Median Tmax increased from 0.5 hours to 3 hours with food. Maximum plasma concentrations and AUC0-inf decreased by approximately 49% and 16% with food, respectively.
Pirfenidone is excreted predominantly as metabolite 5-carboxy-pirfenidone, mainly in the urine (approximately 80% of the dose). The majority of Esbriet was excreted as the 5-carboxy metabolite (approximately 99.6% of that recovered).
/MILK/ A study with radio-labeled pirfenidone in rats has shown that pirfenidone or its metabolites are excreted in milk. It is not known whether Esbriet is excreted in human milk.
... This study aimed to evaluate the pharmacokinetics and urinary excretion of pirfenidone and its major metabolite 5-carboxy-pirfenidone in healthy Chinese subjects under fed conditions. 20 healthy subjects of either sex were recruited in this randomized, single-center, and open-label, single ascending doses (200, 400, and 600 mg) and multiple doses (400 mg, 3 times daily) study. Safety was assessed by adverse events, ECGs, vital signs, and clinical laboratory parameters. Blood and urine samples were analyzed with a validated LC/MS method. Pirfenidone was safe and well tolerated. After single-dose administration, pirfenidone was rapidly absorbed with a mean Tmax of 1.8-2.2 hr and a mean half life of 2.1-2.4 hr. 5-carboxy-pirfenidone was rapidly formed with a mean Tmax of 1.5-2.2 hr and a mean half life of 2.1-2.6 hr. Cmax and AUC for both parent and metabolite were dose proportional over the 200-600 mg dose range. No gender effect was found. In the steady state, the accumulation index (R) estimated for the 3 dosing intervals ranged from 1.1 to 1.5 for both pirfenidone and 5-carboxy-pirfenidone, indicating that the exposure of pirfenidone and 5-carboxy-pirfenidone increased slightly with repeated dosing, but half life and CL/F remained unchanged. Metabolism is the primary mechanism of drug clearance of pirfenidone. About 87.76% of the administered pirfenidone was excreted in urine in the form of 5-carboxy-pirfenidone, while only 0.6159% of the administered pirfenidone was detected as the unchanged form in urine.

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Metabolism / Metabolites
According to _in vitro_ studies, about 70-80% of pirfenidone metabolism is mediated by CYP1A2, as well as some minor contributions from CYP2C9, 2C19, 2D6, and 2E1. Four metabolites have been detected after oral administration of pirfenidone. _In vitro_ data suggest that metabolites are not expected to be pharmacologically active at observed metabolite concentrations. The exact metabolic pathways of pirfenidone have not been fully characterized; however, one of the pathways involve CYP1A2-mediated 5-hydroxylation and subsequent oxidation to form 5-carboxy pirfenidone. In humans, only pirfenidone and 5-carboxy pirfenidone are present in plasma in significant quantities. The mean metabolite-to-parent ratio ranged from approximately 0.6 to 0.7.
Pirfenidone is excreted predominantly as metabolite 5-carboxy-pirfenidone, mainly in the urine (approximately 80% of the dose). The majority of Esbriet was excreted as the 5-carboxy metabolite (approximately 99.6% of that recovered).
In vitro profiling studies in hepatocytes and liver microsomes have shown that Esbriet is primarily metabolized in the liver by CYP1A2 and multiple other CYPs (CYP2C9, 2C19, 2D6, and 2E1). Oral administration of Esbriet results in the formation of four metabolites. In humans, only pirfenidone and 5-carboxy-pirfenidone are present in plasma in significant quantities. The mean metabolite-to-parent ratio ranged from approximately 0.6 to 0.7. No formal radiolabeled studies have assessed the metabolism of pirfenidone in humans. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations.

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Biological Half-Life
The mean terminal half-life is approximately three hours in healthy subjects.
The mean terminal half-life is approximately 3 hours in healthy subjects.
... This study aimed to evaluate the pharmacokinetics and urinary excretion of pirfenidone and its major metabolite 5-carboxy-pirfenidone in healthy Chinese subjects under fed conditions. 20 healthy subjects of either sex were recruited in this randomized, single-center, and open-label, single ascending doses (200, 400, and 600 mg) and multiple doses (400 mg, 3 times daily) study. ... After single-dose administration, pirfenidone was rapidly absorbed with a mean ... half life of 2.1-2.4 hr. 5-carboxy-pirfenidone was rapidly formed with ... a mean half life of 2.1-2.6 hr. ...

Toxicity Summary
IDENTIFICATION AND USE: Pirfenidone is a white solid. It is used as medication for the treatment of idiopathic pulmonary fibrosis. HUMAN EXPOSURE AND TOXICITY: Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be associated with difficulty breathing or wheezing have been reported with use of pirfenidone in the post-marketing setting. ANIMAL STUDIES: In a 24-month carcinogenicity study in rats, pirfenidone caused statistically significant dose-related increases of the combination of hepatocellular adenoma and carcinoma in male rats at doses of 750 mg/kg and above (AUC exposure approximately 1.9 times adult exposure at the MRDD). There were statistically significant increases of the combination of hepatocellular adenoma and carcinoma and the combination of uterine adenocarcinoma and adenoma at a dose of 1500 mg/kg/day (AUC exposure approximately 3.0 times adult exposure at the MRDD). In a 24-month carcinogenicity study in mice, pirfenidone caused statistically significant dose-related increases of the combination of hepatocellular adenoma and carcinoma and hepatoblastoma in male mice at doses of 800 mg/kg and above (AUC exposure approximately 0.4 times adult exposure at the MRDD). There were statistically significant dose-related increases of the combination of hepatocellular adenoma and carcinoma in female mice at doses of 2000 mg/kg and above (AUC exposure approximately 0.7 times adult exposure at the MRDD). Pirfenidone had no effects on fertility and reproductive performance in rats at dosages up to 1000 mg/kg/day (approximately 3 times the MRDD in adults on a mg/sq m basis). A fertility and embryo-fetal development study with rats and an embryo-fetal development study with rabbits that received oral doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults (on mg/sq m basis at maternal doses up to 1000 and 300 mg/kg/day, respectively) revealed no evidence of impaired fertility or harm to the fetus due to pirfenidone. In the presence of maternal toxicity, acyclic/irregular cycles were seen in rats at doses approximately equal to and higher than the MRDD in adults (on a mg/sq m basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal development study, prolongation of the gestation period, decreased numbers of live newborn, and reduced pup viability and body weights were seen in rats at an oral dosage approximately 3 times the MRDD in adults (on a mg/sq m basis at a maternal dose of 1000 mg/kg/day). Pirfenidone was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacteria, a chromosomal aberration test in Chinese hamster lung cells, and a micronucleus test in mice. No genotoxic effects were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically.

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Hepatotoxicity
In large randomized controlled trials, serum aminotransferase elevations more than 3 times the upper limit of normal (ULN) occurred in 4% of pirfenidone- compared to less than 1% of placebo-treated patients. The elevations were generally asymptomatic and short lived, resolving with or without dose modification and requiring drug discontinuation in approximately 1% of patients. Despite the frequency of serum enzyme elevations during therapy, clinically apparent liver injury was not reported in preregistration studies. Nevertheless, since the general availability of pirfenidone in the United States and during years of clinical use elsewhere, there have been isolated case reports of clinically apparent liver injury due to pirfenidone, some of which were severe and even fatal. The latency to onset ranged from one month to one year and the injury was usually hepatocellular or mixed. Immunoallergic features were not common.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Protein Binding
At a dose range of 1 to 10 μg/mL, pirfenidone was approximately 58% bound to human plasma proteins, mainly to serum albumin.

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Interactions
Concomitant use of pirfenidone and CYP1A2 inducers may result in decreased exposure to and reduced efficacy of pirfenidone. The manufacturer of pirfenidone recommends that potent CYP1A2 inducers be avoided during pirfenidone therapy.
Concomitant use of pirfenidone with agents or a combination of agents that are potent or moderate inhibitors of both CYP1A2 and one or more other CYP isoenzymes involved with pirfenidone metabolism (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be avoided.
Concomitant administration of a single dose of pirfenidone with the potent CYP1A2 inhibitor fluvoxamine (initially 50 mg daily, titrated upward to 150 mg daily for 10 days) in nonsmokers and smokers increased pirfenidone exposure approximately fourfold in nonsmokers and sevenfold in smokers.
Concomitant administration of pirfenidone (single 801-mg dose on day 6) with the moderate CYP1A2 inhibitor ciprofloxacin (750 mg twice daily on days 2-7) increased the systemic exposure to pirfenidone by 81%. Pirfenidone dosage should be reduced if used concomitantly with ciprofloxacin at a dosage of 750 mg twice daily. No initial dosage adjustment is recommended if pirfenidone is used concomitantly with ciprofloxacin at a dosage of 250 or 500 mg once daily; however, patients receiving such concomitant therapy should be monitored closely for adverse effects.
For more Interactions (Complete) data for Pirfenidone (8 total), please visit the HSDB record page.

[1]. Pirfenidone inhibits TGF-beta expression in malignant glioma cells. Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7.

[2]. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level. Eur J Pharmacol. 2002 Jun 20;446(1-3):177-85.

[3]. Inhibition of Pirfenidone on TGF-beta2 induced proliferation, migration and epithlial-mesenchymal transitionof human lens epithelial cells line SRA01/04. PLoS One. 2013;8(2):e56837.

[4]. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis. Respir Res. 2014 Feb 8;15:16.

[5]. Limited fibrosis accompanies triple-negative breast cancer metastasis in multiple model systems and is not a preventive target. Oncotarget. 2018 May 4;9(34):23462-23481.

Therapeutic Uses
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Pirfenidone is included in the database.
Esbriet is indicated for the treatment of idiopathic pulmonary fibrosis (IPF). /Included in US product label/
/EXPL THER/ Left ventricular remodeling is a frequent complication of hypertension with no therapeutic treatment available for the subsequent onset of myocardial fibrosis. Pirfenidone is an antifibrotic small-molecular-size drug with anti-inflammatory properties that is used as a treatment for fibrotic diseases, but its effects on hypertension-induced myocardial fibrosis are unknown. Therefore, we tested whether pirfenidone could ameliorate hypertension-induced left ventricular remodeling and whether hypertension-induced NLRP3 (Nod-like receptor pyrin domain containing 3), a critical protein in NLRP3 inflammasome formation, is involved in the therapeutic mechanism. A TAC-induced mouse model of hypertension and left ventricular hypertrophy was treated with pirfenidone, and survival, collagen deposition by histopathologic examination, heart function by echocardiography, concentrations of fibrosis-related inflammatory cytokines TGF-beta1, IL-1beta in heart homogenate and in vitro cell cultures by ELISA, levels of ROS and inflammatory cells by flow cytometry, and levels of NLRP3 by Western blotting and immunohistochemistry were measured. Pirfenidone increased the survival rate and attenuated myocardial fibrosis and inflammatory mediators in the TAC-induced hypertension-complicated left ventricular remodeling mouse model. The inhibition of NLRP3 expression by pirfenidone attenuated the expression of IL-1beta and IL-1beta-induced inflammatory and profibrotic responses. Pirfenidone may be useful in the treatment of hypertension-induced myocardial fibrosis by inhibiting NLRP3-induced inflammation and fibrosis.
/EXPL THER/ Systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) has become the leading SSc-related cause of death. Although various types of immunosuppressive therapy have been attempted for patients with SSc-ILD, no curative or effective treatment strategies for SSc-ILD have been developed. Therefore, management of patients with SSc-ILD remains a challenge. Here, we report a Chinese, female, SSc-ILD patient who was negative for Scl-70 and showed an excellent response to pirfenidone without obvious adverse effects. She had been suffered from dry cough and exertional dyspnea for 2 months. The chest computed tomography manifestation was consistent with a pattern of fibrotic nonspecific interstitial pneumonia. The pulmonary function test showed isolated impaired diffusion. After 11 weeks of administration of pirfenidone, the dry cough and dyspnea had disappeared. Both of the lung shadows and the pulmonary diffusion function were improved. Pirfenidone might be an effective option for early SSc-ILD treatment. A well-controlled clinical trial is expected in the future.

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Drug Warnings
Elevations in serum transaminase (ALT and/or AST) concentrations exceeding 3 times the upper limit of normal (ULN) have occurred in patients receiving pirfenidone; concomitant elevations in bilirubin concentrations have been reported rarely. ALT or AST elevations of at least 3 times the ULN were reported in 3.7% of patients receiving pirfenidone compared with 0.8% of patients receiving placebo in clinical studies; ALT or AST elevations of 10 times the ULN or greater occurred in 0.3% of pirfenidone-treated patients. Increases in liver enzymes were reversible following dosage modification or interruption of therapy. No cases of liver transplant or death due to liver failure related to pirfenidone use have been reported to date; however, the manufacturer states that the combination of transaminase elevations and hyperbilirubinemia without evidence of obstruction is generally recognized as an important predictor of severe liver injury possibly resulting in death or the need for liver transplant in some patients. Liver function tests including ALT, AST, and bilirubin concentrations should be performed prior to initiation of pirfenidone therapy, monthly for the first 6 months, and then every 3 months thereafter. Interruption of therapy and/or dosage reduction may be necessary in patients experiencing liver enzyme elevations.
Cigarette smoking reduces peak plasma concentrations and systemic exposure to pirfenidone by 32 and 54%, respectively. The manufacturer recommends that patients be encouraged to stop smoking prior to initiation of pirfenidone and to avoid smoking during therapy.
There are no adequate and well-controlled studies of Esbriet in pregnant women. Pirfenidone was not teratogenic in rats and rabbits. Because animal reproduction studies are not always predictive of human response, Esbriet should be used during pregnancy only if the benefit outweighs the risk to the patient.
Adverse effects reported in 10% or more of patients receiving pirfenidone and at an incidence greater than with placebo include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia, gastroesophageal reflux disease (GERD), sinusitis, insomnia, decreased weight, and arthralgia.
For more Drug Warnings (Complete) data for Pirfenidone (16 total), please visit the HSDB record page.

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Pharmacodynamics
Pirfenidone is a novel agent with anti-inflammatory, antioxidant, and antifibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF).

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Pirfenidone (AMR69) is an anti-fibrotic and anti-inflammatory small-molecule agent [1][2][3][4]
- Its mechanism of action involves inhibiting the expression of pro-fibrotic cytokines (TGF-β) and pro-inflammatory cytokines (TNF-α), suppressing cell proliferation, migration, and EMT in fibrotic-related cells [1][2][3][4]
- Pirfenidone (AMR69) exhibits in vitro anti-fibrotic activity in lens epithelial cells and fibrocytes, and in vivo anti-fibrotic effects in bleomycin-induced murine pulmonary fibrosis [3][4]
- It has no significant inhibitory effect on triple-negative breast cancer cell proliferation, migration, or metastasis-related fibrosis in animal models [5]
- Pirfenidone (AMR69) is widely used as a tool compound to study fibrosis-related diseases, including pulmonary fibrosis and ocular fibrosis [3][4]

C12H11NO

185.22

185.084

53179-13-8

40632

White to light yellow solid powder

1.1±0.1 g/cm3

329.1±15.0 °C at 760 mmHg

96-97ºC

152.7±11.6 °C

0.0±0.7 mmHg at 25°C

1.592

1.82

22

0

1

1

14

285

0

ISWRGOKTTBVCFA-UHFFFAOYSA-N

InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3

5-methyl-1-phenylpyridin-2-one

S-7701, AMR-69; S 7701, AMR69; S7701, AMR-69; AMR 69; Pirfenidone; trade name: Pirespa; Pirfenex; Deskar, Esbriet; Etuary.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.75 mg/mL (14.85 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.75 mg/mL (14.85 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.08 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.08 mg/mL (11.23 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 6 中的溶解度: 2% DMSO+30% PEG 300+ddH2O:10 mg/mL

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配方 7 中的溶解度: 9.09 mg/mL (49.08 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶 (<60°C).

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配方 8 中的溶解度: 6.67 mg/mL (36.01 mM) in Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 9 中的溶解度: 20 mg/mL (107.98 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。