阿格列汀 | 850649-61-5

• 物质功能分类: 生物化工 - 抑制剂 - 蛋白酶体(Proteases)
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 阿格列汀
• 中文别名: 阿洛利停
• 英文名称: alogliptin
• 英文别名: (R)-2-((6-(3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile；2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]benzonitrile；2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)benzonitrile；2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}-methyl)benzonitrile；2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl}methyl)benzonitrile；2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile
• CAS: 850649-61-5
• 化学式: C₁₈H₂₁N₅O₂
• 分子量: 339.397
• InChiKey: ZSBOMTDTBDDKMP-OAHLLOKOSA-N

物化性质

• 熔点：
  127 - 129°C
• 沸点：
  519.2±60.0 °C(Predicted)
• 密度：
  1.342
• 闪点：
  267.8℃
• 溶解度：
  可溶于氯仿（少许）、乙酸乙酯（少许）、甲醇（少许）
• 蒸汽压力：
  3.11X10-12 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable if stored as directed; avoid strong oxidizing agents
• 分解：
  Thermal decomposition may produce toxic gases such as carbon monoxide, carbon dioxide, and nitrogen oxides.
• 解离常数：
  pKa = 9.47 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  93.7
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

阿格列汀不经历广泛的代谢。检测到的两个次要代谢物是去甲基化阿格列汀（不到母体化合物的1%）和乙酰化阿格列汀（不到母体化合物的6%）。去甲基化代谢物是活性的，是DPP-4的抑制剂。乙酰化代谢物是不活性的。参与阿格列汀代谢的细胞色素酶是CYP2D6和CYP3A4，但这种情况发生的程度很小。大约10-20%的剂量通过细胞色素酶在肝脏中代谢。

Alogliptin does not undergo extensive metabolism. Two minor metabolites that were detected are N-demethylated alogliptin (<1% of parent compound) and N-acetylated alogliptin (<6% of parent compound). The N-demethylated metabolite is active and an inhibitor of DPP-4. The N-acetylated metabolite is inactive. Cytochrome enzymes that are involved with the metabolism of alogliptin are CYP2D6 and CYP3A4 but the extent to which this occurs is minimal. Approximately 10-20% of the dose is hepatically metabolized by cytochrome enzymes.

来源:DrugBank

代谢

在给予口服[14C]阿洛格列汀后，检测到两种次要代谢物，N-去甲基化代谢物M-I（小于母体化合物的1%）和N-乙酰化阿洛格列汀代谢物M-II（小于母体化合物的6%）。M-I是一个活性代谢物，是一种类似于母体的DPP-4抑制剂；M-II对DPP-4或其他DPP相关酶没有显示出抑制作用。体外数据显示CYP2D6和CYP3A4参与了阿洛格列汀有限的代谢。阿洛格列汀主要以（R）-对映体（>99%）存在，在体内很少或没有对（S）-对映体的手性转换。（S）-对映体在25毫克剂量下无法检测到。

Two minor metabolites were detected following administration of an oral dose of [14C] alogliptin, N-demethylated, M-I (<1% of the parent compound), and N-acetylated alogliptin, M-II (<6% of the parent compound). M-I is an active metabolite and is an inhibitor of DPP-4 similar to the parent molecule; M-II does not display any inhibitory activity toward DPP-4 or other DPP-related enzymes. In vitro data indicate that CYP2D6 and CYP3A4 contribute to the limited metabolism of alogliptin. Alogliptin exists predominantly as the (R)-enantiomer (>99%) and undergoes little or no chiral conversion in vivo to the (S)-enantiomer. The (S)-enantiomer is not detectable at the 25 mg dose.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴别人和使用：阿洛格列汀是一种二肽基肽酶-4（DPP-4）抑制剂，作为饮食和运动的辅助手段，用于改善2型糖尿病成年患者的血糖控制；但不用于治疗1型糖尿病或糖尿病酮症酸中毒。人体暴露和毒性：在临床试验中，接受每日25毫克阿洛格列汀的患者报告的不良反应包括胰腺炎（0.2%）、过敏反应（0.6%）、血清病的一次事件、鼻咽炎（4.4%）、低血糖（1.5%）、头痛（4.2%）和上呼吸道感染（4.2%）。在老年患者中，阿洛格列汀引起的低血糖发生率增加到5.4%。在上市后，接受阿洛格列汀治疗的患者报告了急性胰腺炎和严重的过敏反应。这些反应包括过敏性休克、血管性水肿和严重的皮肤不良反应，包括史蒂文斯-约翰逊综合征。在接受Nesina治疗的患者的上市后报告中，有致命和非致命的肝功能衰竭。动物研究：在大鼠的生育研究中，阿洛格列汀在最高500毫克/千克的剂量下，对早期胚胎发育、交配或生育没有不良影响，或者是基于血浆药物暴露（AUC）的大约172倍的临床剂量。在器官形成期给予怀孕兔和大鼠的阿洛格列汀在最高200毫克/千克和500毫克/千克的剂量下不具有致畸性，或者是基于血浆药物暴露（AUC）的149倍和180倍的临床剂量。从妊娠第6天到哺乳第20天给予怀孕大鼠的阿洛格列汀最高250毫克/千克（大约是临床暴露的95倍基于AUC）的剂量，没有对发育中的胚胎造成伤害，也没有对后代的生长和发展产生不利影响。在给怀孕大鼠口服给药后，观察到阿洛格列汀转移到胎儿。阿洛格列汀以2:1的比例分泌在哺乳大鼠的乳汁中。在小鼠给药50、150或300毫克/千克阿洛格列汀两年后，或直到大约是最大推荐临床剂量25毫克的51倍基于AUC暴露下，没有观察到与药物相关的肿瘤。阿洛格列汀在 Ames 测试中使用 S. typhimurium 和 E. coli 或小鼠淋巴瘤细胞的细胞遗传学分析中，无论是否经过代谢激活，都不是致突变或致裂变的。阿洛格列汀在小鼠体内微核研究中呈阴性。

IDENTIFICATION AND USE: Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; but not for treatment of type 1 diabetes or diabetic ketoacidosis. HUMAN EXPOSURE AND TOXICITY: During clinical trials patients receiving alogliptin 25 mg daily reported adverse reactions including pancreatitis (0.2%), hypersensitivity reactions (0.6%), a single event of serum sickness, nasopharyngitis (4.4%), hypoglycemia (1.5%), headache (4.2%) and upper respiratory tract infection (4.2%). In elderly patients the incidence of hypoglycemia with alogliptin increased to 5.4%. Postmarketing, patients taking alogliptin reported acute pancreatitis and serious hypersensitivity reactions. These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking Nesina. ANIMAL STUDIES: In a fertility study in rats, alogliptin had no adverse effects on early embryonic development, mating or fertility at doses up to 500 mg/kg, or approximately 172 times the clinical dose based on plasma drug exposure (AUC). Alogliptin administered to pregnant rabbits and rats during the period of organogenesis was not teratogenic at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times, respectively, the clinical dose based on plasma drug exposure (AUC). Doses of alogliptin up to 250 mg/kg (approximately 95 times clinical exposure based on AUC) given to pregnant rats from gestation Day 6 to lactation Day 20 did not harm the developing embryo or adversely affect growth and development of offspring. Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma. No drug-related tumors were observed in mice after administration of 50, 150 or 300 mg/kg alogliptin for two years, or up to approximately 51 times the maximum recommended clinical dose of 25 mg, based on AUC exposure. Alogliptin was not mutagenic or clastogenic, with and without metabolic activation, in the Ames test with S. typhimurium and E. coli or the cytogenetic assay in mouse lymphoma cells. Alogliptin was negative in the in vivo mouse micronucleus study.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

alogliptin导致肝损伤是罕见的。在大规模临床试验中，血清酶升高不常见（1%至3%），并不比对照臂或安慰剂更高。在这些研究中，没有报告出现黄疸的临床明显肝损伤的病例。自从获得许可以来，已经向FDA和赞助商报告了alogliptin引起的血清酶升高和急性肝炎的病例，包括急性肝衰竭。这些病例在文献中没有报道，临床特征也尚未确定。其他DPP-4抑制剂（如sitagliptin和saxagliptin）也报告了临床明显的急性肝损伤病例。发病潜伏期通常在开始用药后2至12周内，肝酶升高的模式通常是肝细胞型。免疫过敏特征常常存在。大多数病例在停药后过程自我限制，并且迅速逆转。

Liver injury due to alogliptin is rare. In large clinical trials, serum enzyme elevations were uncommon (1% to 3%) and no greater than with comparator arms or placebo. In these studies, no instances of clinically apparent liver injury with jaundice were reported. Since licensure, instances of serum enzyme elevations and acute hepatitis including acute liver failure attributed to alogliptin have been reported to the FDA and the sponsor. These cases have not been reported in the literature and the clinical features have not been defined. Cases of clinically apparent acute liver injury have been reported with other DPP-4 inhibitors such as sitagliptin and saxagliptin. The latency to onset was typically within 2 to 12 weeks of starting and the pattern of liver enzyme elevations was usually hepatocellular. Immunoallergic features were often present. Most cases were self-limited in course and rapidly reversed once the medication was stopped.

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：目前没有关于在哺乳期间使用阿格列汀的临床信息。在哺乳新生儿或早产儿时，可能更倾向于使用另一种药物。在母亲使用阿格列汀治疗期间，建议监测母乳喂养婴儿的血糖。 ◉ 对母乳喂养婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the clinical use of alogliptin during breastfeeding. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. Monitoring of the breastfed infant's blood glucose is advisable during maternal therapy with alogliptin. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

当alogliptin与胰岛素促泌剂（例如，磺酰脲类药物）或胰岛素联合使用时，与磺酰脲类药物或胰岛素单药治疗相比，低血糖的发生率增加。因此，接受alogliptin治疗的患者可能需要减少同时使用的胰岛素促泌剂或胰岛素的剂量，以降低低血糖的风险。

When alogliptin is used in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin, the incidence of hypoglycemia is increased compared with sulfonylurea or insulin monotherapy. Therefore, patients receiving alogliptin may require a reduced dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

NESINA的药代动力学在健康受试者和2型糖尿病患者中也显示出相似性。当给予健康受试者和2型糖尿病患者单次口服剂量高达800mg时，alogliptin的峰值血浆浓度（中位数Tmax）在给药后1到2小时出现。Alogliptin的积累最小。NESINA的绝对生物利用度大约为100%。食物不影响alogliptin的吸收。

The pharmacokinetics of NESINA was also shown to be similar in healthy subjects and in patients with type 2 diabetes. When single, oral doses up to 800 mg in healthy subjects and type 2 diabetes patients are given, the peak plasma alogliptin concentration (median Tmax) occurred 1 to 2 hours after dosing. Accumulation of aloglipin is minimal. The absolute bioavailability of NESINA is approximately 100%. Food does not affect the absorption of alogliptin.

来源:DrugBank

吸收、分配和排泄

• 消除途径

肾脏排泄（76%）和粪便（13%）。60%至71%的剂量以未改变的药物形式在尿液中排出。

Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在健康受试者单次静脉输注12.5毫克阿格列汀后，终末相的分布体积为417升，表明该药物在组织中分布良好。

Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues.

来源:DrugBank

吸收、分配和排泄

• 清除

肾清除率 = 9.6 L/h（这个值表明有一定的活性肾小管分泌）；系统清除率 = 14.0 L/h。

Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.

来源:DrugBank

吸收、分配和排泄

(14C)阿格列汀衍生的放射性主要通过肾脏排泄(76%),粪便中回收13%,总计回收了89%的给药放射性剂量。阿格列汀的肾脏清除率(9.6 L/hr)表明存在一定的肾小管分泌活动,系统清除率为14.0 L/hr。

The primary route of elimination of (14C) alogliptin-derived radioactivity occurs via renal excretion (76%) with 13% recovered in the feces, achieving a total recovery of 89% of the administered radioactive dose. The renal clearance of alogliptin (9.6 L/hr) indicates some active renal tubular secretion and systemic clearance was 14.0 L/hr.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S24/25
• 海关编码：
  29335990
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储于室温、干燥且密封的环境中。

制备方法与用途

阿罗格列汀是一种口服降糖药，是二肽基肽-4（DPP-4）酶的选择性抑制剂。

靶点	值
DPP-4 (293E 细胞裂解物)	2.93 nM

反应信息

• 作为反应物：
  描述：

  阿格列汀 在 fluorosulfuryl azide 、 potassium hydrogencarbonate 作用下， 以 甲基叔丁基醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以90%的产率得到2-[[6-[(3R)-3-azidopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile
  参考文献：
  名称：

  使用重氮化试剂进行功能筛选的模块化点击化学库

  摘要：

  点击化学是一个概念，其中模块化合成用于快速找到具有所需特性的新分子1。铜 (i) 催化的叠氮化物 - 炔烃环加成 (CuAAC) 三唑环化和硫 (vi) 氟化物交换 (SuFEx) 催化被广泛认为是点击反应 2-4，可快速获得其产品，产率接近 100%，同时在很大程度上是正交的到其他反应。然而，在 CuAAC 反应的情况下，由于其潜在的毒性和制备过程中涉及的爆炸风险，叠氮化物试剂的可用性受到限制。在这里，我们报告了另一种添加到点击反应家族的反应：由伯胺形成叠氮化物，伯胺是最丰富的官能团之一。该反应仅使用一当量的简单重氮化物质，氟磺酰叠氮化物 6-11 (FSO2N3)，并且能够以安全实用的方式在 96 孔板上制备 1,200 多种叠氮化物。这种可靠的转化是 CuAAC 三唑环化的有力工具，这是目前使用最广泛的点击反应。该方法极大地扩展了可接近的叠氮化物和 1,2,3-三唑的数量，鉴于 CuAAC

  DOI：

  10.1038/s41586-019-1589-1
• 作为产物：
  描述：

  (R)-1-(3-(2-cyanobenzyl)-1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)piperidine-3-carboxamide 在 吡啶 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 水 、 异丙醇 为溶剂， 反应 3.0h， 以87.2%的产率得到阿格列汀
  参考文献：
  名称：

  阿格列汀的不对称合成工艺的开发和放大

  摘要：

  阿格列汀（1）苯甲酸酯是一种有效的，高度选择性的丝氨酸蛋白酶二肽基肽酶IV抑制剂，已获美国FDA批准用于治疗2型糖尿病。在此，我们报告了一种更具成本效益的方法，其中包括钌催化的不对称氢化反应，然后进行2-（（（6-氯-3-甲基-2,4-二氧代-3,4-二氢嘧啶-1（2 H）-基）甲基）苄腈（10）在后期引入手性氨基部分。在温和且特殊的条件下，使用廉价且容易获得的烟酰胺（6）制备手性氨基哌啶核和碘代苯二乙酸盐（PIDA），使我们可以使用1 具有极佳的总产量和可与原始工艺生产的产品相媲美的质量。

  DOI：

  10.1021/acs.oprd.0c00544

文献信息

• Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines
  作者：Shoujun Sun、Bing Gao、Junyu Chen、K. Barry Sharpless、Jiajia Dong

  DOI：10.1002/anie.202105583

  日期：2021.9.20

  Fluorosulfuryl isocyanate (FSI, FSO2NCO) is established as a reliable bis-electrophilic linker for stepwise attachment of an alcohol bearing module to an amine bearing module and thence a new module RO-C(=O)-NH-SO2-NR′R′′ is created. FSI's isocyanate motif fuses directly and quickly with alcohols and phenols, affording fluorosulfuryl carbamates in nearly quantitative yield. A new reagent and process

  氟磺酰异氰酸酯 (FSI, FSO 2 NCO) 被确立为可靠的双亲电连接剂，用于将含醇模块逐步连接至含胺模块，从而形成新模块 RO-C(=O)-NH-SO 2 -NR 'R'' 已创建。 FSI 的异氰酸酯基序直接快速地与醇和酚融合，以几乎定量的产率提供氟磺酰氨基甲酸酯。还开发了一种新的试剂和工艺，可将 FSI 衍生的氟硫酰氨基甲酸酯片段传递给胺。鉴于不同产品的结构非常复杂，步骤 1 所得的 S VI -F 基序非常稳定。在与胺的第 2 步反应中，仅用水即可获得 SN 连接产物的最佳产率。这种“水上”界面反应现象至关重要，揭示了 S VI -F 探针潜在的体内蛋白质共价捕获的潜在反应性，这在当今的药物发现中非常重要。 SuFEx 化学的范围因此大大扩展，并且轻松进入这些磷酸盐样连接应该对跨不同领域的点击化学有用。
• Late-Stage Carbon Isotope Exchange of Aryl Nitriles through Ni-Catalyzed C–CN Bond Activation
  作者：Sean W. Reilly、Yu-hong Lam、Sumei Ren、Neil A. Strotman

  DOI：10.1021/jacs.1c01454

  日期：2021.3.31

  strategy employs labeled Zn(CN)2 to facilitate enrichment using the nonlabeled parent compound as the starting material, eliminating de novo synthesis for precursor development. A broad substrate scope encompassing multiple pharmaceuticals is disclosed, including the preparation of [14C] belzutifan to illustrate the exceptional functional group tolerance and utility of this labeling approach. Preliminary

  描述了使用 Ni 膦催化剂和 BPh 3与芳基、杂芳基和烯基腈进行13 CN 和14 CN 交换的简便一锅法。这种后期碳同位素交换 (CIE) 策略采用标记的 Zn(CN) 2来促进使用未标记的母体化合物作为起始材料的富集，从而消除了前体开发的从头合成。公开了涵盖多种药物的广泛底物范围，包括制备 [ 14 C] belzutifan 以说明这种标记方法的特殊官能团耐受性和实用性。初步实验和计算研究表明路易斯酸 BPh 3对氧化加成步骤并不重要，而是在促进 Ni 上的 CN 交换方面发挥作用。这种 CIE 方法显着减少了制备用于临床开发的14 C 标记示踪剂所涉及的合成步骤和放射性废物。
• Novel phenyl-substituted imidazolidines, process for preparation thereof, medicaments comprising said compounds and use thereof
  申请人：JAEHNE Gerhard

  公开号：US20110178134A1

  公开（公告）日：2011-07-21

  The invention relates to compounds of formula (I) wherein the groups have stated meanings, and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.

  本发明涉及具有所述意义的公式（I）的化合物，以及它们的生理相容性盐。所述化合物适用于例如作为抗肥胖药物和治疗心血管代谢综合征。
• AZOLOPYRIDIN-3-ONE DERIVATIVES AS INHIBITORS OF LIPASES AND PHOSPHOLIPASES
  申请人：Petry Stefan

  公开号：US20130157941A1

  公开（公告）日：2013-06-20

  The present invention relates to azolopyridin-3-one derivatives of the general formula (I) with the meanings specified in the description, to their pharmaceutically usable salts and to their use as drug substances.

  本发明涉及通式（I）所示的咪唑吡啶-3-酮衍生物，其含义如描述中所指定的，以及它们的药用盐和作为药物物质的用途。
• BILE ACID RECYCLING INHIBITORS FOR TREATMENT OF GASTROINTESTINAL INFECTIONS
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20150119345A1

  公开（公告）日：2015-04-30

  Provided herein are methods for treating or preventing gastrointestinal and/or liver infections utilizing bile acid transport inhibitors and/or enteroendocrine peptide enhancing agents and/or FXR agonists. Also provided herein are methods for increasing the levels of an enteroendocrine peptide or hormone in an individual suffering from a gastrointestinal infection or liver infection utilizing bile acid transport inhibitors and/or enteroendocrine peptide enhancing agents and/or FXR agonists.

  本文提供了利用胆汁酸转运抑制剂和/或肠内分泌肽增强剂和/或FXR激动剂治疗或预防胃肠和/或肝感染的方法。本文还提供了利用胆汁酸转运抑制剂和/或肠内分泌肽增强剂和/或FXR激动剂增加患有胃肠感染或肝感染的个体体内肠内分泌肽或激素水平的方法。