体外活性：洛替泼诺具有代谢不稳定的功能，即 17β-酯，旨在在体循环中快速失活。依碳氯替泼诺表现出的结合亲和力是地塞米松的 4.3 倍，这两种化合物的 Hill 因子接近 1，而 PJ90 和 PJ91 对受体没有表现出任何亲和力。激酶测定： 细胞测定：

静脉注射 5 mg/kg 依碳氯替泼诺的犬显示出 2.8 小时的终末半衰期、3.7 L/kg 的分布容积和 0.9 L/h/kg 的全身清除率。尿液中未发现。狗口服药物（5毫克/公斤），血浆中仅含有代谢物——没有完整的药物——这表明存在显着的首过影响。

Absorption, Distribution and Excretion
Loteprednol etabonate (LE) demonstrates good ocular permeation properties as it is lipid soluble, allowing the agent to penetrate into cells with relative ease. Results from the ocular administration of loteprednol in normal, healthy volunteers have shown that there are low or undetectable concentrations of either unchanged material or its metabolite. Following twice-daily unilateral topical ocular dosing of LE for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all time points. These finds suggest that limited, if any, systemic absorption of LE occurs.
Following systemic administration to rats, loteprednol etabonate is eliminated primarily via the biliary/faecal route, with most of the dose eliminated in the form of the metabolite, PJ-90.
The only data available regarding the volume of distribution of loteprednol etabonate (LE) is the volume of distribution the agent demonstrated when administered to dogs - a value of 3.7 L/kg. It has been shown, however, that the topical ocular administration of LE distributes preferentially into the cellular components of blood.
Loteprednol etabonate was slowly hydrolyzed in liver at clearance rates of 0.21 +/- 0.04 and 2.41 +/- 0.13 ml/h/kg in the liver and plasma, respectively.

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Metabolism / Metabolites
Loteprednol etabonate (LE) is readily and extensively metabolized to two inactive metabolites, PJ-90 (Δ1-cortienic acid) and PJ-91 (Δ1-cortienic acid etabonate). Metabolism occurs locally in ocular tissues, and to the extent that loteprednol etabonate reaches the systemic circulation, likely the liver and other tissues into which it distributes. In particular, studies have demonstrated that LE (chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-3-oxoandrosta-1,4-diene) is rapidly hydrolyzed at the location of its 17beta-chloromethyl ester function by paraoxonase 1 in human plasma at the site of administration at the level of the affected eye tissue to the 17beta-carboxylate PJ-91 metabolite and PJ-90 metabolite. Both metabolites are considered inactive.

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Biological Half-Life
The terminal half-life of loteprednol etabonate as determined when administered intravenously at a dose of 5 mg/kg in the dog animal model is 2.8 hours.

Protein Binding
Strong protein binding of approximately 98% for loteprednol etabonate facilitates little pharmacodynamic action and/or adverse effects on the part of the agent in the systemic circulation.

[1]. Noble S, Goa KL. Loteprednol etabonate: clinical potential in the management of ocular inflammation. BioDrugs. 1998 Oct;10(4):329-39.

[2]. Loteprednol etabonate: a soft steroid for the treatment of allergic diseases of the airways. Drugs Today (Barc). 2000 May;36(5):313-20.

[3]. Howes JF. Loteprednol etabonate: a review of ophthalmic clinical studies. Pharmazie. 2000 Mar;55(3):178-83.

[4]. Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9.

[5]. Comstock TL, Decory HH. Advances in corticosteroid therapy for ocular inflammation: loteprednol etabonate. Int J Inflam. 2012;2012:789623.

Loteprednol etabonate is an etabonate ester, an 11beta-hydroxy steroid, a steroid ester, an organochlorine compound, a steroid acid ester and a 3-oxo-Delta(1),Delta(4)-steroid. It has a role as an anti-inflammatory drug. It is functionally related to a loteprednol.
Loteprednol Etabonate (LE) is a topical corticoid anti-inflammatory. It is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitides. As a nasal spray, it can be used for the treatment and management of seasonal allergic rhinitis. Most prescription LE products, however, tend to be indicated for the treatment of post-operative inflammation and pain following ocular surgery. A number of such new formulations that have been approved include Kala Pharmaceutical's Inveltys - the first twice-daily (BID) ocular corticosteroid approved for this indication, designed specifically to enhance patient compliance and simplified dosing compared to all other similar ocular steroids that are dosed four times daily. Moreover, LE was purposefully engineered to be a 'soft drug', one that is designed to be active locally at the site of administration and then rapidly metabolized to inactive components after eliciting its actions at the desired location, thereby subsequently minimizing the chance for adverse effects.
Loteprednol Etabonate is the etabonate salt form of loteprednol, an ophthalmic analog of the corticosteroid prednisolone with anti-inflammatory activity. Loteprednol etabonate exerts its effect by interacting with specific intracellular receptors and subsequently binds to DNA to modify gene expression. This results in an induction of the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Loteprednol etabonate specifically induces phospholipase A2 inhibitory proteins (collectively called lipocortins), which inhibit the release of arachidonic acid, thereby inhibiting the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes.
An androstadiene derivative corticosteroid that is used as an ANTI-ALLERGIC AGENT for the treatment of inflammatory and allergic eye conditions.
See also: Loteprednol (has active moiety); Loteprednol etabonate; tobramycin (component of).

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Drug Indication
A number of prescription loteprednol etabonate ophthalmic products are specifically indicated for the treatment of post-operative inflammation and pain following ocular surgery.
FDA Label

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Mechanism of Action
Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly associated with inflammation. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established. Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms. In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. The use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery.

C24H31CLO7

466.95

466.175

82034-46-6

Loteprednol Etabonate-d5;2026643-11-6;Loteprednol Etabonate-d3

444025

White to off-white solid powder

1.3±0.1 g/cm3

600.1±55.0 °C at 760 mmHg

220.5-223.5ºC

316.7±31.5 °C

0.0±3.9 mmHg at 25°C

1.571

3.17

99.13

1

7

7

32

882

7

CCOC(=O)O[C@@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)C=C[C@]34C)O)C)C(=O)OCCl

DMKSVUSAATWOCU-HROMYWEYSA-N

InChI=1S/C24H31ClO7/c1-4-30-21(29)32-24(20(28)31-13-25)10-8-17-16-6-5-14-11-15(26)7-9-22(14,2)19(16)18(27)12-23(17,24)3/h7,9,11,16-19,27H,4-6,8,10,12-13H2,1-3H3/t16-,17-,18-,19+,22-,23-,24-/m0/s1

chloromethyl (8S,9S,10R,11S,13S,14S,17R)-17-ethoxycarbonyloxy-11-hydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17-carboxylate

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 (5.35 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 储备液加入900 μL 玉米油中，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。