DPP-4 (IC50 = 2.93 nM)

Alogliptin shows more than 10,000 fold selectivity over the closely related serine proteases DPP-8 and DPP-9 and is a potent (IC50 < 10 nM) inhibitor of DPP-4[1].Even at concentrations up to 30μM, compound 10 does not inhibit CYP-450 enzymes or block the hERG channel[2].

Analogliptin has an absolute oral bioavailability of 45%, 86%, and 72% to 88% in rats, dogs, and monkeys, respectively. Alogliptin administered orally results in plasma DPP-4 inhibition in rats, dogs, and monkeys within 15 minutes, with maximum inhibition exceeding 90%. The inhibition lasts for 12 hours in rats (43%), 6.5 hours in dogs, and 24 hours in monkeys (> 80%). Rats, dogs, and monkeys with mean alogliptin plasma concentrations (EC50) ranging from 3.4 to 5.6 ng/ml (10.0 to 16.5 nM) exhibit 50% inhibition of DPP-4 activity, according to Emax modeling. Alogliptin, at doses of 0.3, 1, 3, and 10 mg/kg, inhibits plasma DPP-4 in Zucker fa/fa rats (91% to 100% at 2 hours and 20% to 66% at 24 hours), increases plasma GLP-1 (AUC0–20 min increases 2- to 3-fold), increases early-phase insulin secretion (AUC0–20 min increases 1.5–2.6 fold), and decreases blood glucose excursion (31%–67% decrease in AUC0–90 min) following oral glucose challenge. Normoglycemic rats' plasma glucose levels during fasting are unaffected by apelliptin (30 and 100 mg/kg).[3].

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Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by increasing plasma active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide levels. However, the effects of chronic DPP-4 inhibition on in vivo beta-cell function are poorly characterized. We thus evaluated the chronic effects of the DPP-4 inhibitor alogliptin benzoate (formerly SYR-322) on metabolic control and beta-cell function in obese diabetic ob/ob mice. Alogliptin (0.002%, 0.01%, or 0.03%) was administered in the diet to ob/ob mice for 2 days to determine effects on plasma DPP-4 activity and active GLP-1 levels and for 4 weeks to determine chronic effects on metabolic control and beta-cell function. After 2 days, alogliptin dose-dependently inhibited DPP-4 activity by 28-82% and increased active GLP-1 by 3.2-6.4-fold. After 4 weeks, alogliptin dose-dependently decreased glycosylated hemoglobin by 0.4-0.9%, plasma glucose by 7-28% and plasma triglycerides by 24-51%, increased plasma insulin by 1.5-2.0-fold, and decreased plasma glucagon by 23-26%, with neutral effects on body weight and food consumption. In addition, after drug washout, alogliptin (0.03% dose) increased early-phase insulin secretion by 2.4-fold and improved oral meal tolerance (25% decrease in glucose area under the concentration-time curve), despite the lack of measurable plasma DPP-4 inhibition. Importantly, alogliptin also increased pancreatic insulin content up to 2.5-fold, and induced intense insulin staining of islets, suggestive of improved beta-cell function. In conclusion, chronic treatment with alogliptin improved glycemic control, decreased triglycerides, and improved beta-cell function in ob/ob mice, and may exhibit similar effects in patients with type 2 diabetes[4].

DPP-4 Assay: [2]
Solutions of test compounds in varying concentrations (≤10 mM final concentration) were prepared in Dimethyl Sulfoxide (DMSO) and then diluted into assay buffer comprising: 20 mM Tris, pH 7.4; 20 mM KCl; and 0.1 mg/mL BSA. Human DPP-4 (0.1 nM final concentration) was added to the dilutions and pre-incubated for 10 minutes at ambient temperature before the reaction was initiated with A-P-7-amido-4- trifluoromethylcoumarin (AP-AFC; 10 μM final concentration). The total volume of the reaction mixture was 10-100 μL depending on assay formats used (384 or 96 well plates). The reaction was followed kinetically (excitation λ= 400 nm; emission λ= 505 nm) for 5- 10 minutes or an end-point was measured after 10 minutes. Inhibition constants (IC50) were calculated from the enzyme progress curves using standard mathematical models.[2]

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Microsomal Stability: [2]
The test compounds (1 μM) were incubated at 37 °C in phosphate buffer (50 mM, pH 7.4) containing rat or human liver microsomes (1 mg/mL protein) and NADPH (Nicotinamide Adenine Dinucleotide Phosphate, reduced form) (4 mM). The incubation mixtures were quenched with trichloroacetic acid (0.3 M) over 0, 5, 15, 30 minute time-course. Quenched solutions were centrifuged and supernatants were transferred for LC/MS quantitation. The half-life of test compounds was derived from the compound stability curve over the time course.[2]

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Alogliptin (also known as SYR-322) is a novel, potent, selective, and orally bioavailable inhibitor of DPP-4 (serine protease dipeptidyl peptidase IV). With an IC50 value of 2.6 nM, it shows over 10,000-fold selectivity for DPP-4 over DPP-8 and DPP-9, two closely related enzymes. Even at concentrations up to 30 μM, alogliptin does not block the hERG channel or inhibit CYP-450 enzyme activity.

Here researchers reported a newly established cell model system by cloning and transfecting human DPP8/9 genes into HEK 293 cells. We then used this model to evaluate the clinically applied DPP4 inhibitors' effect on DPP8/9, by direct enzymatic activity assay. Given the difference of cellular locations between DPP4 and DPP8/9, we also evaluated the influence of these drugs on intracellular DPP8/9 activity and cell viability by extracellular treatment with different inhibitors.
Results: Direct enzymatic activity assay revealed significant and concentration-dependent inhibition effect of vildagliptin, saxagliptin on DPP8/9. Extracellular incubation of DPP8/9 over expressed cells with sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin, showed only mild inhibition on DPP8/9. Moreover, all of these drugs showed no significant influence on cell viability.
Discussion: The results demonstrated that the DPP8/9 over-expressing cell model system is a very useful and promising system for investigating the selectivity and associated toxicity of DPP4 inhibitors on DPP8/9[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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 0.5% methylcellulose: 30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)