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Loteprednol etabonate
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Looking for Loteprednol etabonate API 82034-46-6?
- Description:
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- API | Excipient name:
- Loteprednol etabonate
- Cas Number:
- 82034-46-6
- DrugBank number:
- DB14596
- Unique Ingredient Identifier:
- YEH1EZ96K6
General Description:
Loteprednol etabonate (LE), with CAS number 82034-46-6, is a solid-state corticosteroid specifically formulated for topical use, demonstrating significant anti-inflammatory properties. This innovative compound is predominantly utilized in ophthalmic solutions for the management of various steroid-responsive inflammatory conditions of the eye, including allergic conjunctivitis, uveitis, and post-operative inflammation following ocular surgery. Notably, it is also available as a nasal spray for treating seasonal allergic rhinitis, expanding its therapeutic utility. LE distinguishes itself as a 'soft drug,' designed for localized action with rapid metabolism to inactive metabolites, thereby minimizing potential systemic side effects and enhancing patient safety. Pharmacodynamically, Loteprednol etabonate exhibits a binding affinity to glucocorticoid receptors approximately 4.3 times greater than that of dexamethasone, establishing its efficacy in inhibiting inflammatory responses. Its mechanism of action involves the suppression of key inflammatory mediators, including prostaglandins and leukotrienes, via the induction of lipocortins that inhibit phospholipase A2, thereby controlling the biosynthesis of these potent inflammatory agents. Clinically, LE is indicated for post-operative inflammation and pain, with recent formulations such as Kala Pharmaceuticals' Inveltys providing twice-daily dosing to improve patient adherence compared to traditional four-times-daily corticosteroids. The compound’s pharmacokinetic profile reveals rapid ocular absorption with minimal systemic exposure, ensuring localized effects while limiting adverse reactions. With approved international brands including Eysuvis and Loteflam, Loteprednol etabonate represents a significant advancement in corticosteroid therapy, offering effective management of ocular and nasal inflammatory conditions.
| Identification | |||
|---|---|---|---|
| Summary | Loteprednol Etabonate (LE) is a topical corticosteroid with potent anti-inflammatory properties, primarily indicated for treating post-operative inflammation and pain following ocular surgery, as well as various ocular inflammatory conditions. Engineered as a "soft drug," LE is designed for localized action with rapid metabolism to inactive metabolites, minimizing systemic side effects while exhibiting superior ocular and skin permeation. | ||
| Groups | approved | Drug Categories | Adrenal Cortex Hormones, Androstadienes, Androstanes, Androstenes, Anti-Allergic Agents, Corticosteroids, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 Substrates, Fused-Ring Compounds, Immunosuppressive Agents, Steroids |
| Brand Names | Eysuvis, Loteflam | ||
| Properties | |||
| State | solid | ||
| Average Mass | 466.96 | ||
| Chemical Taxonomy | |||
|---|---|---|---|
| Description | This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group. | ||
| Direct-parent | Steroid esters | ||
| Kingdom | Organic compounds | ||
| Superclass | Lipids and lipid-like molecules | ||
| Class | Steroids and steroid derivatives | ||
| Subclass | Steroid esters | ||
| Alternative-parent | Secondary alcohols | ||
| Substituent | Steroid ester | ||
| Pharmacology | |
|---|---|
| Indication | A number of prescription loteprednol etabonate ophthalmic products are specifically indicated for the treatment of post-operative inflammation and pain following ocular surgery . |
| Pharmacodynamics | Loteprednol etabonate (LE) belongs to a unique class of corticosteroids with potent anti-inflammatory effects designed to be active at the site of action . Animal studies have shown that LE has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone . This particular class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body . Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity . Specifically, LE is an ester derivative of one of these analogs, cortienic acid etabonate . In particular, LE possesses a metabolically labile 17 beta-chloromethyl ester function which was designed in order to be hydrolyzed to an inactive carboxylic acid moiety . This inactive metabolite is more hydrophilic and is thus readily eliminated from the body . LE also exhibits good ocular permeation properties and good skin permeation properties . |
| 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 . |
| Absorption | 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 . |
| Volume of Distribution | 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 . |
| 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 . |
| Metabolism | 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 . |
| Route of Elimination | 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 . |
| 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 . |
| Clearance | 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 . |
| Toxicity | The most common adverse drug reactions reported during clinical trials for the medication were eye pain and posterior capsular opacification, both of which may also be the consequence of the very surgical procedures performed on the eye(s) . The agent is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug . The medication is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child to the agent . Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay . Overdose is not expected to be likely to occur after ocular administration . |
Loteprednol etabonate is a type of Hormones
Hormones are a vital category of pharmaceutical Active Pharmaceutical Ingredients (APIs) that play a crucial role in regulating various physiological processes in the human body. These chemical messengers are produced by endocrine glands and are responsible for maintaining homeostasis, growth, metabolism, and reproductive functions.
Pharmaceutical hormones are synthetic or naturally derived compounds that mimic the structure and function of endogenous hormones. They are widely used in the treatment of hormonal disorders, such as hypothyroidism, diabetes, and hormonal imbalances.
Common examples of hormone APIs include insulin, thyroid hormones (such as levothyroxine), glucocorticoids (such as prednisone), and sex hormones (such as estrogen and testosterone). These APIs are carefully synthesized, purified, and formulated to ensure optimal efficacy, stability, and bioavailability.
Hormone APIs are typically produced through advanced chemical synthesis or biotechnological processes, involving the use of genetically engineered microorganisms or mammalian cell cultures. Stringent quality control measures and regulatory guidelines ensure the purity, potency, and safety of hormone APIs.
Pharmaceutical companies and research institutions invest significant resources in developing hormone APIs, as they are fundamental for the treatment of various endocrine disorders. The demand for hormone APIs continues to grow, driven by the rising prevalence of hormonal diseases and an aging population.
In conclusion, hormone APIs are essential components of pharmaceuticals that help restore hormonal balance and alleviate various endocrine disorders. Their significance in healthcare makes them a crucial category in the pharmaceutical industry.
