DPP-4 (IC50 = 2.93 nM)

体外活性：阿格列汀（也称为 SYR-322）是一种新型、有效、口服生物可利用的选择性 DPP-4（丝氨酸蛋白酶二肽基肽酶 IV）抑制剂，IC50 值为 2.6 nM，其活性大于 10,000 倍。 DPP-4 的选择性高于密切相关的 DPP-8 和 DPP-9。是2010年在日本上市的抗糖尿病药； 2013 年，FDA 批准了该药物的三种剂型：单独使用的商品名为 Nesina，与二甲双胍联合使用的商品名为 Kazano，与吡格列酮联合使用的商品名为 Oseni。与其他治疗 2 型糖尿病的药物一样，阿格列汀不会降低心脏病发作和中风的风险。阿格列汀和其他格列汀通常与二甲双胍联合用于单独使用二甲双胍无法充分控制糖尿病的患者。激酶测定：阿格列汀（也称为 SYR-322）是一种新型、有效、口服生物可利用的选择性 DPP-4（丝氨酸蛋白酶二肽基肽酶 IV）抑制剂，IC50 值为 2.6 nM，选择性超过 10,000 倍DPP-4 优于密切相关的 DPP-8 和 DPP-9。阿格列汀不是 CYP-450 酶的抑制剂，浓度高达 30 μM 时不会阻断 hERG 通道。

阿格列汀（SYR-322）可产生剂量依赖性的葡萄糖耐量改善，并提高雌性 Wistar 脂肪大鼠的血浆胰岛素水平。急性给予阿格列汀会导致血浆 DPP-4 活性显着降低，并增加血浆活性 GLP-1。阿格列汀在 0.3 mg/kg 及更高剂量时可改善葡萄糖耐量，血浆 IRI 呈剂量依赖性增加，表明葡萄糖耐量改善是由于阿格列汀增强胰岛素分泌的能力所致。

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二肽基肽酶-4（DPP-4）抑制剂通过提高血浆活性胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽水平来改善2型糖尿病患者的血糖控制。然而，慢性DPP-4抑制对体内β细胞功能的影响尚不清楚。因此，我们评估了DPP-4抑制剂苯甲酸阿格列汀（前身为SYR-322）对肥胖糖尿病ob/ob小鼠代谢控制和β细胞功能的慢性影响。在ob/ob小鼠的饮食中给予Alogliptin（0.002%、0.01%或0.03%）2天，以确定对血浆DPP-4活性和活性GLP-1水平的影响，并给予4周，以确定其对代谢控制和β细胞功能的慢性影响。2天后，阿格列汀剂量依赖性地抑制DPP-4活性28-82%，并将活性GLP-1增加3.2-6.4倍。4周后，阿格列汀剂量依赖性地将糖化血红蛋白降低0.4-0.9%，血糖降低7-28%，甘油三酯降低24-51%，血浆胰岛素增加1.5-2.0倍，血浆胰高血糖素降低23-26%，对体重和食物消耗具有中性影响。此外，在药物洗脱后，阿格列汀（0.03%剂量）将早期胰岛素分泌增加了2.4倍，并改善了口服餐耐受性（浓度-时间曲线下葡萄糖面积减少了25%），尽管缺乏可测量的血浆DPP-4抑制作用。重要的是，阿格列汀还将胰腺胰岛素含量增加了2.5倍，并诱导胰岛强烈的胰岛素染色，表明β细胞功能得到改善。总之，阿格列汀的慢性治疗改善了ob/ob小鼠的血糖控制，降低了甘油三酯，改善了β细胞功能，并可能在2型糖尿病患者中表现出类似的效果[4]。

DPP-4检测：[2]
在二甲基亚砜（DMSO）中制备不同浓度（≤10mM终浓度）的试验化合物溶液，然后稀释到包含20mM Tris、pH 7.4的测定缓冲液中；20mM氯化钾；将人DPP-4（终浓度为0.1 nM）加入稀释液中，在环境温度下预孵育10分钟，然后用A-P-7-酰胺基-4-三氟甲基香豆素（AP-AFC；终浓度为10μM）引发反应。反应混合物的总体积为10-100μL，具体取决于所使用的测定格式（384或96孔板）。对反应进行动力学跟踪（激发λ=400 nm；发射λ=505 nm）5-10分钟，或在10分钟后测量终点。使用标准数学模型从酶进程曲线计算抑制常数（IC50）。[2]

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肝微粒体稳定性：[2]
试验化合物（1μM）在37°C下在含有大鼠或人肝微粒体（1 mg/mL蛋白质）和NADPH（烟酰胺腺嘌呤二核苷酸磷酸盐，还原形式）（4 mM）的磷酸盐缓冲液（50 mM，pH 7.4）中孵育。在0、5、15、30分钟的时间过程中，用三氯乙酸（0.3M）淬灭孵育混合物。将淬火溶液离心，转移上清液进行LC/MS定量。试验化合物的半衰期由化合物随时间变化的稳定性曲线得出。[2]

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阿格列汀（也称为 SYR-322）是一种新型、有效、选择性、口服生物可利用的 DPP-4（丝氨酸蛋白酶二肽基肽酶 IV）抑制剂。它的 IC50 值为 2.6 nM，对 DPP-4 的选择性比 DPP-8 和 DPP-9（两种密切相关的酶）高 10,000 倍以上。即使浓度高达 30 μM，阿格列汀也不会阻断 hERG 通道或抑制 CYP-450 酶活性。

在这里，研究人员通过克隆人DPP8/9基因并将其转染到HEK 293细胞中，报告了一种新建立的细胞模型系统。然后，我们使用该模型通过直接酶活性测定来评估临床应用的DPP4抑制剂对DPP8/9的影响。鉴于DPP4和DPP8/9在细胞位置上的差异，我们还评估了这些药物通过不同抑制剂的细胞外处理对细胞内DPP8/9活性和细胞存活率的影响。
结果：直接酶活性测定显示，维达列汀、沙格列汀对DPP8/9具有显著的浓度依赖性抑制作用。DPP8/9过表达细胞与西格列汀、维格列汀、沙格列汀、阿格列汀和利格列汀的细胞外孵育仅显示出对DPP8/9的轻度抑制。此外，所有这些药物对细胞存活率没有显著影响。
讨论：结果表明，DPP8/9过表达细胞模型系统是一个非常有用和有前景的系统，用于研究DPP4抑制剂对DPP8/9的选择性和相关毒性[1]。

db/db mice
76.4 mg/kg/day
oral

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The aim of the present research was to characterize the pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel quinazolinone-based dipeptidyl peptidase-4 (DPP-4) inhibitor. Alogliptin potently inhibited human DPP-4 in vitro (mean IC(50), ~ 6.9 nM) and exhibited > 10,000-fold selectivity for DPP-4 over the closely related serine proteases DPP-2, DPP-8, DPP-9, fibroblast activation protein/seprase, prolyl endopeptidase, and tryptase (IC(50) > 100,000 nM). Absolute oral bioavailability of alogliptin in rats, dogs, and monkeys was 45%, 86%, and 72% to 88%, respectively. After a single oral dose of alogliptin, plasma DPP-4 inhibition was observed within 15 min and maximum inhibition was > 90% in rats, dogs, and monkeys; inhibition was sustained for 12 h in rats (43%) and dogs (65%) and 24 h in monkeys (> 80%). From E(max) modeling, 50% inhibition of DPP-4 activity was observed at a mean alogliptin plasma concentration (EC(50)) of 3.4 to 5.6 ng/ml (10.0 to 16.5 nM) in rats, dogs, and monkeys. In Zucker fa/fa rats, a single dose of alogliptin (0.3, 1, 3, and 10 mg/kg) inhibited plasma DPP-4 (91% to 100% at 2 h and 20% to 66% at 24 h), increased plasma GLP-1 (2- to 3-fold increase in AUC(0-20 min)) and increased early-phase insulin secretion (1.5- to 2.6-fold increase in AUC(0-20 min)) and reduced blood glucose excursion (31%-67% decrease in AUC(0-90 min)) after oral glucose challenge. Alogliptin (30 and 100 mg/kg) had no effect on fasting plasma glucose in normoglycemic rats. In summary, these data suggest that alogliptin is a potent and highly selective DPP-4 inhibitor with demonstrated efficacy in Zucker fa/fa rats and potential for once-daily dosing in humans.[3]

Absorption, Distribution and Excretion
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.
Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.
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.
Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.
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.
Alogliptin does not undergo extensive metabolism and 60% to 71% of the dose is excreted as unchanged drug in the urine.
The absolute bioavailability of NESINA is approximately 100%. Administration of NESINA with a high-fat meal results in no significant change in total and peak exposure to alogliptin. NESINA may therefore be administered with or without food.
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. Alogliptin is 20% bound to plasma proteins.
For more Absorption, Distribution and Excretion (Complete) data for Alogliptin (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
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.
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.

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Biological Half-Life
Terminal half-life = 21 hours
At the maximum recommended clinical dose of 25 mg, Nesina was eliminated with a mean terminal half-life of approximately 21 hours.

Toxicity Summary
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.

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Hepatotoxicity
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.
Likelihood score: E* (unproven but suspected cause of acute, idiosyncratic liver injury).

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Effects During Pregnancy and Lactation
◉ 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.

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Protein Binding
Alogliptin is 20% bound to plasma proteins.

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Interactions
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.

[1]. J Pharmacol Toxicol Methods . 2015 Jan-Feb:71:8-12.

[2]. J Med Chem . 2007 May 17;50(10):2297-300.

[3]. Eur J Pharmacol . 2008 Jul 28;589(1-3):306-14.

[4]. Eur J Pharmacol . 2008 Jul 7;588(2-3):325-32.

Alogliptin is a piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of type 2 diabetes. It has a role as an EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor and a hypoglycemic agent. It is a nitrile, a member of piperidines, a member of pyrimidines and a primary amino compound. It is a conjugate base of an alogliptin(1+).
Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013.
Alogliptin is a Dipeptidyl Peptidase 4 Inhibitor. The mechanism of action of alogliptin is as a Dipeptidyl Peptidase 4 Inhibitor.
Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other oral hypoglycemic agents. Alogliptin has been reported to cause liver injury, but the characteristics and details of the injury have not been defined in the published literature.
Alogliptin is a selective, orally bioavailable, pyrimidinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. In addition to its effect on glucose levels, alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.
See also: Alogliptin Benzoate (has salt form); Alogliptin; metformin hydrochloride (component of).

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Drug Indication
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
FDA Label
Vipidia is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control (see sections 4. 4, 4. 5 and 5. 1 for available data on different combinations).
Treatment of type II diabetes mellitus

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Mechanism of Action
Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.
Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

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Therapeutic Uses
Hypoglycemic Agents
Nesina is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. /Included in US product label/
A single-dose, open-label study was conducted to evaluate the pharmacokinetics of alogliptin 50 mg in patients with chronic renal impairment compared with healthy subjects. In patients with mild renal impairment (creatinine clearance (CrCl) =60 to <90 mL/min), an approximate 1.2-fold increase in plasma AUC of alogliptin was observed. Because increases of this magnitude are not considered clinically relevant, dose adjustment for patients with mild renal impairment is not recommended. In patients with moderate renal impairment (CrCl =30 to <60 mL/min), an approximate two-fold increase in plasma AUC of alogliptin was observed. To maintain similar systemic exposures of Nesina to those with normal renal function, the recommended dose is 12.5 mg once daily in patients with moderate renal impairment. In patients with severe renal impairment (CrCl =15 to <30 mL/min) and ESRD (CrCl <15 mL/min or requiring dialysis), an approximate three- and four-fold increase in plasma AUC of alogliptin were observed, respectively. Dialysis removed approximately 7% of the drug during a three-hour dialysis session. Nesina may be administered without regard to the timing of the dialysis. To maintain similar systemic exposures of Nesina to those with normal renal function, the recommended dose is 6.25 mg once daily in patients with severe renal impairment, as well as in patients with ESRD requiring dialysis.

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Drug Warnings
/BOXED WARNING/ WARNING: RISK OF LACTIC ACIDOSIS. Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, Kazano (alogliptin and metformin hydrochloride) should be discontinued and the patient hospitalized immediately. /Alogliptin and metformin hydrochloride combination product/
FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. ... FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report. The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer. At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels. ...
There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking Nesina, although some of the reports contain insufficient information necessary to establish the probable cause.
There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Nesina. These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. If a serious hypersensitivity reaction is suspected, discontinue Nesina, assess for other potential causes for the event and institute alternative treatment for diabetes.
For more Drug Warnings (Complete) data for Alogliptin (18 total), please visit the HSDB record page.

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Pharmacodynamics
Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.

C18H21N5O2

339.391643285751

339.17

C, 63.70; H, 6.24; N, 20.64; O, 9.43

850649-61-5

Alogliptin Benzoate;850649-62-6;Alogliptin-d3;1133421-35-8;Alogliptin-13C,d3 benzoate;Alogliptin-13C,d3;1246817-18-4

11450633

White to off-white solid powder

0.6

93.7

1

5

3

25

622

1

CN1C(=O)C=C(N(C1=O)CC2=CC=CC=C2C#N)N3CCC[C@H](C3)N

ZSBOMTDTBDDKMP-OAHLLOKOSA-N

InChI=1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1

2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile

SYR 322; Alogliptin; SYR-322; 850649-61-5; alogliptina; (R)-2-((6-(3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile; Alogliptin [INN]; UNII-JHC049LO86; alogliptine; alogliptinum; SYR322; Brand name: Nesina; Kazano; Oseni

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: ≥ 2.5 mg/mL (7.37 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 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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 2 中的溶解度: ≥ 2.5 mg/mL (7.37 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 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，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 3 中的溶解度: ≥ 2.5 mg/mL (7.37 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 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 0.5% methylcellulose: 30 mg/mL

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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。