在体外，ERTUGLIFLIZIN (PF-04971729) 抑制 SGLT2 的效果是 SGLT1 的 2000 倍以上 [3]。

在 FXR 的后期，ertugliflozin (PF-04971729) 表现出浓度依赖性糖尿 [3]。

Absorption, Distribution and Excretion
After administering single doses of 5 mg and 15 mg ertugliflozin under fasted conditions, the median Tmax was one hour. Plasma Cmax and AUC of ertugliflozin increase dose-proportionally. Following administration of a 15 mg dose, the Cmax was 268 ng/mL and the AUC was 1193 ng h/mL. The absolute oral bioavailability of ertugliflozin following administration of a 15 mg dose was approximately 100%, though it is reported to range from 70% to 90%. Administration of ertugliflozin with a high-fat and high-calorie meal decreases ertugliflozin Cmax by 29%. It prolongs Tmax by one hour but does not alter AUC compared to the fasted state. The observed effect of food on ertugliflozin pharmacokinetics is not considered clinically relevant, and ertugliflozin may be administered with or without food.
Following administration of an oral [¹⁴C]-ertugliflozin solution to healthy subjects, approximately 40.9% and 50.2% of the drug-related radioactivity was eliminated in feces and urine, respectively. Only 1.5% of the administered dose was excreted as unchanged ertugliflozin in urine and 33.8% as unchanged ertugliflozin in feces, which is likely due to biliary excretion of glucuronide metabolites and subsequent hydrolysis to form the parent compound.
The volume of distribution following oral administration was 215.3 L. The mean steady-state volume of distribution of ertugliflozin following an intravenous dose is 85.5 L.
The apparent total plasma clearance rate after a single dose administration of 15 mg ertugliflozin is 178.7 mL/min. The mean systemic plasma clearance following an intravenous 100 µg dose was 11.2 L/hr.

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Metabolism / Metabolites
Ertugliflozin mainly undergoes O-glucuronidation mediated by UGT1A9 and UGT2B7 to form two pharmacologically inactive glucuronides. About 12% of the drug undergoes CYP-mediated oxidative metabolism. Several metabolites have been found in plasma, feces, and urine. In plasma, the unchanged form of ertugliflozin was found to be the major component of the administered dose.

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Biological Half-Life
The terminal elimination half-life of ertugliflozin ranges from 11 to 17 hours. The mean elimination half-life in T2DM patients with normal renal function was estimated to be 16.6 hours based on the population pharmacokinetic analysis.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of ertugliflozin during breastfeeding. Ertugliflozin is 94% protein bound in plasma, so it is unlikely to pass into breastmilk in clinically important amounts. The manufacturer does not recommend ertugliflozin during breastfeeding because of a theoretical risk to the infant's developing kidney. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ 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
Ertugliflozin is 93.6% bound to plasma proteins. Plasma protein binding is independent of ertugliflozin plasma concentrations and is not meaningfully altered in patients with renal or hepatic impairment. The blood-to-plasma concentration ratio of ertugliflozin is 0.66.

[1]. Mascitti V, et al. Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem. 2011 Apr 28;54(8):2952-60.
[2]. Miao Z, et al. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos. 2013 Feb;41(2):445-56.
[3]. Kalgutkar AS, et al. Preclinical species and human disposition of PF-04971729, a selective inhibitor of the sodium-dependent glucose cotransporter 2 and clinical candidate for the treatment of type 2 diabetes mellitus. Drug Metab Dispos. 2011 Sep;39(9):1609-19.

Ertugliflozin is a diarylmethane.
Ertugliflozin is a sodium-dependent glucose cotransporter-2 (SGLT2) inhibitor used to treat type II diabetes mellitus. It works to block glucose reabsorption from the glomerulus. Ertugliflozin was first approved by the FDA in December 2017. It was also approved by the European Commission in March 2018.
See also: Ertugliflozin pidolate (active moiety of); Ertugliflozin; METformin Hydrochloride (component of); Ertugliflozin; Sitagliptin Phosphate (component of).

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Drug Indication
Ertugliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus (T2DM). It is also available in combination with either [metformin] or [sitagliptin]. Ertugliflozin is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.
Steglatro is indicated in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: as monotherapy in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications. in addition to other medicinal products for the treatment of diabetes.
Treatment of type II diabetes mellitus

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Mechanism of Action
Kidneys play an integral role in glucose homeostasis. After being filtered into urine within the nephron, most of the plasma glucose is reabsorbed through two types of sodium-dependent glucose cotransporters (SGLTs), SGLT1 and SGLT2, expressed in proximal renal tubules. More specifically, SGLT2 is responsible for 80–90% of renal glucose reabsorption while SGLT1 is responsible for the remaining 10-20%. Under physiological conditions, less than one percent of glucose is excreted in urine. In the case of hyperglycemia, SGLTs become saturated and the renal threshold for urinary glucose excretion is increased. Kidneys respond to an elevated threshold for glycosuria by elevating glucose reabsorption and increasing maximum glucose reabsorptive capacity. Ertugliflozin is an inhibitor of SGLT2 that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.

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Pharmacodynamics
Ertugliflozin causes a dose-dependent increase in urinary glucose excretion and an increase in urinary volume in patients with T2DM.

C22H25CLO7

436.89

436.128

1210344-57-2

Ertugliflozin L-pyroglutamic acid;1210344-83-4;Ertugliflozin-d5;1298086-22-2

44814423

White to off-white solid powder

1.5±0.1 g/cm3

630.5±55.0 °C at 760 mmHg

335.1±31.5 °C

0.0±1.9 mmHg at 25°C

1.652

6.49

108.61

4

7

6

30

586

5

ClC1C([H])=C([H])C(=C([H])C=1C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])C([H])([H])[H])[C@]12[C@@]([H])([C@]([H])([C@@]([H])([C@](C([H])([H])O[H])(C([H])([H])O1)O2)O[H])O[H])O[H]

MCIACXAZCBVDEE-CUUWFGFTSA-N

InChI=1S/C22H25ClO7/c1-2-28-16-6-3-13(4-7-16)9-14-10-15(5-8-17(14)23)22-20(27)18(25)19(26)21(11-24,30-22)12-29-22/h3-8,10,18-20,24-27H,2,9,11-12H2,1H3/t18-,19-,20+,21-,22-/m0/s1

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: ≥ 2.08 mg/mL (4.76 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DMSO储备液加入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: ≥ 2.08 mg/mL (4.76 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 20.8 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: ≥ 2.08 mg/mL (4.76 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 储备液加入到 900 μL 玉米油中并混合均匀。

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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。