| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
Loteprednol etabonate (Lotemax; Alrex; HGP-1; Loterox; Locort; P-5604; HGP1; Lenoxin, CDDD-5604), the esther form of Loteprednol, is a potent glucocorticoid receptor agonist approved as a medication used in treatment of inflammation of the eye due to allergies. Loteprednol possesses a metabolically labile function, the 17beta-ester, that is designed to be rapidly deactivated in the systemic circulation. Loteprednol etabonate exhibits a binding affinity which is 4.3 times that of dexamethasone.
| ln Vitro |
|
||
|---|---|---|---|
| ln Vivo |
Dogs receiving 5 mg/kg of loteprednol etabonate intravenously show a 2.8 h terminal half-life, 3.7 L/kg volume of distribution, and 0.9 L/h/kg total body clearance. not found in the urine. Dogs received the medication orally (5 mg/kg), and the plasma solely contained metabolites—no intact drug—which suggests a substantial first-pass impact.
|
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
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. 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. 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. |
||
| Toxicity/Toxicokinetics |
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. |
||
| References |
|
||
| Additional Infomation |
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. |
| Molecular Formula |
C24H31CLO7
|
|
|---|---|---|
| Molecular Weight |
466.95
|
|
| Exact Mass |
466.175
|
|
| CAS # |
82034-46-6
|
|
| Related CAS # |
Loteprednol Etabonate-d5;2026643-11-6;Loteprednol Etabonate-d3
|
|
| PubChem CID |
444025
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
600.1±55.0 °C at 760 mmHg
|
|
| Melting Point |
220.5-223.5ºC
|
|
| Flash Point |
316.7±31.5 °C
|
|
| Vapour Pressure |
0.0±3.9 mmHg at 25°C
|
|
| Index of Refraction |
1.571
|
|
| LogP |
3.17
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
7
|
|
| Rotatable Bond Count |
7
|
|
| Heavy Atom Count |
32
|
|
| Complexity |
882
|
|
| Defined Atom Stereocenter Count |
7
|
|
| SMILES |
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
|
|
| InChi Key |
DMKSVUSAATWOCU-HROMYWEYSA-N
|
|
| InChi Code |
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
|
|
| Chemical Name |
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
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1416 mL | 10.7078 mL | 21.4156 mL | |
| 5 mM | 0.4283 mL | 2.1416 mL | 4.2831 mL | |
| 10 mM | 0.2142 mL | 1.0708 mL | 2.1416 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA