Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H27ClO5 |
| Molecular Weight | 394.889 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 7 / 7 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@]12C[C@H](O)[C@H]3[C@@H](CCC4=CC(=O)C=C[C@]34C)[C@@H]1CC[C@]2(O)C(=O)OCCl
InChI
InChIKey=YPZVAYHNBBHPTO-MXRBDKCISA-N
InChI=1S/C21H27ClO5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,18(25)27-11-22)20(15,2)10-16(24)17(14)19/h5,7,9,14-17,24,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,17+,19-,20-,21-/m0/s1
| Molecular Formula | C21H27ClO5 |
| Molecular Weight | 394.889 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 7 / 7 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Loteprednol (as the ester loteprednol etabonate) is a corticosteroid used to treat inflammations of the eye. It is marketed by Bausch and Lomb as Lotemax. It 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 conjunctivitis’s. Lotemax is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with Lotemax experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. Lotemax is also indicated for the treatment of post-operative inflammation following ocular surgery. Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, 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. Corticosteroids are capable of producing a rise in intraocular pressure (IOP). Loteprednol etabonate is structurally similar to other corticosteroids. However, the number 20 position ketone group is absent. It is highly lipid soluble, which enhances its penetration into cells. Loteprednol etabonate is synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. Based upon in vivo and in vitro preclinical metabolism studies, loteprednol etabonate undergoes extensive metabolism to inactive carboxylic acid metabolites. Lotemax possesses some adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.
Originator
Sources: http://adisinsight.springer.com/drugs/800003442
Curator's Comment: Loteprednol etabonate is a glucocorticoid receptor agonist that was originally developed by Pharmos Corp as a topical treatment for various ocular inflammatory
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12861354 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | LOTEMAX Approved UseLOTEMAX is indicated for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation. LOTEMAX is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with LOTEMAX experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in IOP (≥10 mmHg) was 1% with LOTEMAX and 6% with prednisolone acetate 1%. LOTEMAX should not be used in patients who require a more potent corticosteroid for this indication. LOTEMAX is also indicated for the treatment of post-operative inflammation following ocular surgery. Launch Date1998 |
|||
| Primary | LOTEMAX Approved UseLOTEMAX is indicated for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation. LOTEMAX is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with LOTEMAX experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in IOP (≥10 mmHg) was 1% with LOTEMAX and 6% with prednisolone acetate 1%. LOTEMAX should not be used in patients who require a more potent corticosteroid for this indication. LOTEMAX is also indicated for the treatment of post-operative inflammation following ocular surgery. Launch Date1998 |
|||
| Primary | LOTEMAX Approved UseLOTEMAX is indicated for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation. LOTEMAX is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with LOTEMAX experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in IOP (≥10 mmHg) was 1% with LOTEMAX and 6% with prednisolone acetate 1%. LOTEMAX should not be used in patients who require a more potent corticosteroid for this indication. LOTEMAX is also indicated for the treatment of post-operative inflammation following ocular surgery. Launch Date1998 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
139 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
400 μg 1 times / day multiple, nasal dose: 400 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
164 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
800 μg 1 times / day multiple, nasal dose: 800 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
414 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
400 μg 1 times / day multiple, nasal dose: 400 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
495 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
800 μg 1 times / day multiple, nasal dose: 800 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
400 μg 1 times / day multiple, nasal dose: 400 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15102872/ |
800 μg 1 times / day multiple, nasal dose: 800 μg route of administration: Nasal experiment type: MULTIPLE co-administered: FLUTICASONE PROPIONATE |
LOTEPREDNOL ETABONATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Intraocular pressure elevation from topical difluprednate use. | 2010-12 |
|
| Rate and risk factors for cataract formation and extraction after Descemet stripping endothelial keratoplasty. | 2010-11 |
|
| Loteprednol and tobramycin in combination: a review of their impact on current treatment regimens. | 2010-04 |
|
| Post-penetrating keratoplasty glaucoma. | 2008-06-27 |
|
| Treatment of ocular inflammatory conditions with loteprednol etabonate. | 2008-04 |
|
| Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis. | 2008-01 |
|
| Comparison of ketorolac tromethamine, diclofenac sodium, and loteprednol etabonate in an animal model of ocular inflammation. | 2006-06 |
|
| Can corticosteroids be beaten in future asthma therapy? | 2006-02 |
|
| A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. | 2004-09 |
|
| Possibilities in improvement of glucocorticoid treatments in asthma with special reference to loteprednol etabonate. | 2004-05 |
|
| Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. | 2004-01 |
|
| Bilateral nongranulomatous anterior uveitis associated with bimatoprost. | 2003-11 |
|
| Comparison of the clinical efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension in the conjunctival allergen challenge model. | 2002-06 |
|
| Asthma therapy in the new millennium. | 2002-06 |
|
| Loteprednol etabonate. Alrex, Lotemax, Loteprednol, Loterox. | 2002 |
Sample Use Guides
Apply one to two drops of LOTEMAX (loteprednol etabonate ophthalmic suspension) into the conjunctival sac of the affected eye four times daily. During the initial treatment within the first week, the dosing may be increased, up to 1 drop every hour, if necessary.
Route of Administration:
Other
| Substance Class |
Chemical
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Z8CBU6KR16
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