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Identification
Name Loteprednol
Accession Number DB00873 (APRD01078)
Type small molecule
Groups approved
Description

Loteprednol (as Loteprednol Etabonate) is a topical corticoid antiinflammatory. 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, is used for the treatment and management of seasonal allergic rhinitis.
Structure Thumb
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Display: 2D Structure | 3D Structure
Synonyms
Loteprednol Etabonate
Salts Not Available
Brand names
Name Company
Alrex
Loteflam
Lotemax Bausch and Lomb
Brand mixtures
Brand Name Ingredients
Zylet 0.5% loteprednol etabonate + 0.3% tobramycin
Categories
  • Anti-inflammatory Agents
  • Anti-Allergic Agents
CAS number 82034-46-6
Weight Average: 394.889
Monoisotopic: 394.154701681
Chemical Formula C21H27ClO5
InChI Key InChIKey=YPZVAYHNBBHPTO-MXRBDKCISA-N
InChI
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
Plain Text
IUPAC Name
chloromethyl (1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-2,15-dimethyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-14-carboxylate
SMILES
[H][C@@]12CC[C@](O)(C(=O)OCCl)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication As an ophthalmic it is used 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, used for the treatment and management of seasonal allergic rhinitis.
Pharmacodynamics Loteprednol etabonate (LE) is a "soft" steroid belonging to a unique class of glucocorticoids. 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. Loteprednol etabonate has good ocular permeation properties and good skin permeation properties similar to "hard" steroids. It is used as a topical agent for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis and iritis.
Mechanism of action Loteprednol etabonate (LE) is a "soft" steroid belonging to a unique class of glucocorticoids. Loteprednol etabonate is structurally similar to other glucocorticoids. 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. It first binds to the type II glucocorticoid receptor. 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.
Absorption Very limited systemic absorption, but good absorption at the point of delivery.
Volume of distribution Not Available
Protein binding Not Available
Metabolism The drugs 17 beta-chloromethyl ester function is hydrolyzed to an inactive carboxylic acid moiety.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Adverse effects include abnormal vision / blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, injection, and photophobia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bausch and lomb inc
  • Pharmos corp
Packagers
Dosage forms
Form Route Strength
Suspension Ophthalmic
Prices Not Available
Patents
Country Patent Number Approved Expires (estimated)
United States 5540930 1993-10-25 2013-10-25
United States 4996335 1995-03-09 2012-03-09
Canada 2174550 2002-10-01 2014-10-21
Properties
State solid
Experimental Properties
Property Value Source
melting point 220-224 °C Not Available
water solubility 5 mg/mL Not Available
logP 3.4 Not Available
Predicted Properties
Property Value Source
water solubility 3.36e-02 g/l ALOGPS
logP 2.2 ALOGPS
logP 2.52 ChemAxon
logS -4.1 ALOGPS
pKa (strongest acidic) 12.01 ChemAxon
pKa (strongest basic) -2.9 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 83.83 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 102.65 ChemAxon
polarizability 41.29 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Pubmed
External Links
Resource Link
KEGG Drug D01689 Link_out
ChEBI 50848 Link_out
ChEMBL 50848 Link_out
Therapeutic Targets Database DAP001045 Link_out
PharmGKB PA164764569 Link_out
RxList http://www.rxlist.com/cgi/generic2/lotemax.htm Link_out
Drugs.com http://www.drugs.com/cdi/loteprednol-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Loteprednol Link_out
ATC Codes
  • S01BA14
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (1.1 MB)
MSDS show (57.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Druzgala P, Hochhaus G, Bodor N: Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: loteprednol etabonate. J Steroid Biochem Mol Biol. 1991 Feb;38(2):149-54. Pubmed
  2. Bodor N, Buchwald P: Corticosteroid design for the treatment of asthma: structural insights and the therapeutic potential of soft corticosteroids. Curr Pharm Des. 2006;12(25):3241-60. Pubmed
  3. Szelenyi I, Hochhaus G, Heer S, Kusters S, Marx D, Poppe H, Engel J: Loteprednol etabonate: a soft steroid for the treatment of allergic diseases of the airways. Drugs Today (Barc). 2000 May;36(5):313-20. Pubmed
  4. Samudre SS, Lattanzio FA Jr, Williams PB, Sheppard JD Jr: Comparison of topical steroids for acute anterior uveitis. J Ocul Pharmacol Ther. 2004 Dec;20(6):533-47. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19