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Identification
NameLoteprednol
Accession NumberDB00873  (APRD01078)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
LoteprednolGermanNot Available
LoteprednolFrenchNot Available
LoteprednolSpanishNot Available
LoteprednolumLatinNot Available
Salts
Name/CAS Structure Properties
Loteprednol Etabonate
Thumb Not applicable DBSALT000930
Brand names
NameCompany
AlrexBausch and Lomb
LoteflamCipla Pharmaceuticals Limited
LotemaxBausch and Lomb
Brand mixtures
Brand NameIngredients
Zylet0.5% loteprednol etabonate + 0.3% tobramycin
Categories
CAS number82034-46-6
WeightAverage: 394.889
Monoisotopic: 394.154701681
Chemical FormulaC21H27ClO5
InChI KeyInChIKey=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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassAndrogens and Derivatives
Direct parentAndrogens and Derivatives
Alternative parentsHydroxysteroids; Ketosteroids; Cyclohexanols; Tertiary Alcohols; Ketones; Carboxylic Acid Esters; Cyclic Alcohols and Derivatives; Enolates; Polyamines; Ethers; Organochlorides; Alkyl Chlorides
Substituentscyclohexanol; cyclic alcohol; tertiary alcohol; secondary alcohol; carboxylic acid ester; ketone; enolate; carboxylic acid derivative; polyamine; ether; organohalogen; organochloride; alcohol; carbonyl group; alkyl halide; alkyl chloride
Classification descriptionThis compound belongs to the androgens and derivatives. These are hydroxylated C19 steroid hormones. They are known to favour the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
Pharmacology
IndicationAs 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.
PharmacodynamicsLoteprednol 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 actionLoteprednol 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.
AbsorptionVery limited systemic absorption, but good absorption at the point of delivery.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

The drugs 17 beta-chloromethyl ester function is hydrolyzed to an inactive carboxylic acid moiety.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAdverse 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9884
Blood Brain Barrier + 0.9294
Caco-2 permeable + 0.5426
P-glycoprotein substrate Substrate 0.7489
P-glycoprotein inhibitor I Non-inhibitor 0.6379
P-glycoprotein inhibitor II Non-inhibitor 0.6419
Renal organic cation transporter Non-inhibitor 0.7633
CYP450 2C9 substrate Non-substrate 0.862
CYP450 2D6 substrate Non-substrate 0.914
CYP450 3A4 substrate Substrate 0.794
CYP450 1A2 substrate Non-inhibitor 0.8987
CYP450 2C9 substrate Non-inhibitor 0.8866
CYP450 2D6 substrate Non-inhibitor 0.872
CYP450 2C19 substrate Non-inhibitor 0.9233
CYP450 3A4 substrate Non-inhibitor 0.5687
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8468
Ames test Non AMES toxic 0.8574
Carcinogenicity Non-carcinogens 0.9436
Biodegradation Not ready biodegradable 0.9614
Rat acute toxicity 2.2305 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9647
hERG inhibition (predictor II) Non-inhibitor 0.5773
Pharmacoeconomics
Manufacturers
  • Bausch and lomb inc
  • Pharmos corp
Packagers
Dosage forms
FormRouteStrength
SuspensionOphthalmic
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States55409301993-10-252013-10-25
United States49963351995-03-092012-03-09
Canada21745502002-10-012014-10-21
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point220-224 °CNot Available
water solubility5 mg/mLNot Available
logP3.4Not Available
Predicted Properties
PropertyValueSource
water solubility3.36e-02 g/lALOGPS
logP2.2ALOGPS
logP2.52ChemAxon
logS-4.1ALOGPS
pKa (strongest acidic)12.01ChemAxon
pKa (strongest basic)-2.9ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area83.83ChemAxon
rotatable bond count3ChemAxon
refractivity102.65ChemAxon
polarizability41.29ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Pubmed
External Links
ResourceLink
KEGG DrugD01689
ChEBI50848
ChEMBL
Therapeutic Targets DatabaseDAP001045
PharmGKBPA164764569
RxListhttp://www.rxlist.com/cgi/generic2/lotemax.htm
Drugs.comhttp://www.drugs.com/international/loteprednol.html
WikipediaLoteprednol
ATC CodesS01BA14
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(1.1 MB)
MSDSshow(57.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

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 October 19, 2013 10:39