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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
Loteprednol
Loteprednol
Loteprednol
Loteprednolum
External Identifiers
  • CDDD 5604
  • HGP 1
  • P 5604
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alrexsuspension/ drops2 mg/mLophthalmicSTAT Rx USA LLC1998-03-09Not applicableUs
Alrexsuspension/ drops2 mg/mLophthalmicPhysicians Total Care, Inc.2002-10-17Not applicableUs
Alrexsuspension/ drops2 mg/mLophthalmicBausch & Lomb Incorporated1998-03-09Not applicableUs
Alrexsuspension0.2 %ophthalmicBausch & Lomb Inc2009-06-24Not applicableCanada
Lotemaxsuspension/ drops5 mg/mLophthalmicPhysicians Total Care, Inc.2002-10-17Not applicableUs
Lotemaxgel5 mg/gophthalmicBausch & Lomb Incorporated2012-10-12Not applicableUs
Lotemaxointment5 mg/gophthalmicBausch & Lomb Incorporated2011-04-15Not applicableUs
Lotemaxsuspension0.5 %ophthalmicBausch & Lomb Inc2009-06-24Not applicableCanada
Lotemaxsuspension/ drops5 mg/mLophthalmicBausch & Lomb Incorporated1998-03-09Not applicableUs
Lotemax Gelgel0.5 %ophthalmicBausch & Lomb Inc2015-06-25Not applicableCanada
Lotemax Ointmentointment0.5 %ophthalmicBausch & Lomb Inc2014-10-29Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LoteflamCipla Pharmaceuticals Limited
Brand mixtures
NameLabellerIngredients
ZyletBausch & Lomb Incorporated
Salts
Name/CASStructureProperties
Loteprednol etabonate
82034-46-6
Thumb
  • InChI Key: DMKSVUSAATWOCU-HROMYWEYSA-N
  • Monoisotopic Mass: 466.175831
  • Average Mass: 466.96
DBSALT000930
Categories
UNIIZ8CBU6KR16
CAS number129260-79-3
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[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-diene-14-carboxylate
SMILES
[H][C@@]12CC[C@](O)(C(=O)OCCl)[C@@]1(C)C[[email protected]](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassAndrostane steroids
Direct ParentAndrogens and derivatives
Alternative Parents
Substituents
  • Androgen-skeleton
  • 17-hydroxysteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • 3-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • Delta-1,4-steroid
  • Tertiary alcohol
  • Cyclic alcohol
  • Cyclic ketone
  • Secondary alcohol
  • Ketone
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Halomethane
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl chloride
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier+0.9294
Caco-2 permeable+0.5426
P-glycoprotein substrateSubstrate0.7489
P-glycoprotein inhibitor INon-inhibitor0.6379
P-glycoprotein inhibitor IINon-inhibitor0.6419
Renal organic cation transporterNon-inhibitor0.7633
CYP450 2C9 substrateNon-substrate0.862
CYP450 2D6 substrateNon-substrate0.914
CYP450 3A4 substrateSubstrate0.794
CYP450 1A2 substrateNon-inhibitor0.8987
CYP450 2C9 inhibitorNon-inhibitor0.8866
CYP450 2D6 inhibitorNon-inhibitor0.872
CYP450 2C19 inhibitorNon-inhibitor0.9233
CYP450 3A4 inhibitorNon-inhibitor0.5687
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8468
Ames testNon AMES toxic0.8574
CarcinogenicityNon-carcinogens0.9436
BiodegradationNot ready biodegradable0.9614
Rat acute toxicity2.2305 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9647
hERG inhibition (predictor II)Non-inhibitor0.5773
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bausch and lomb inc
  • Pharmos corp
Packagers
Dosage forms
FormRouteStrength
Suspensionophthalmic0.2 %
Suspension/ dropsophthalmic2 mg/mL
Gelophthalmic5 mg/g
Ointmentophthalmic5 mg/g
Suspensionophthalmic0.5 %
Suspension/ dropsophthalmic5 mg/mL
Gelophthalmic0.5 %
Ointmentophthalmic0.5 %
Suspension/ dropsophthalmic
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2174550 No2002-10-012014-10-21Canada
US4996335 No1995-03-092012-03-09Us
US5540930 No1993-10-252013-10-25Us
US5800807 No1997-01-292017-01-29Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point220-224 °CNot Available
water solubility5 mg/mLNot Available
logP3.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0336 mg/mLALOGPS
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 Area83.83 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity102.65 m3·mol-1ChemAxon
Polarizability41.29 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Pavesio CE, Decory HH: Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9. doi: 10.1136/bjo.2007.132621. Epub 2008 Feb 1. [PubMed:18245274 ]
External Links
ATC CodesS01BA14
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (1.1 MB)
MSDSDownload (57.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, 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 grow...
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
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:2004037 ]
  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:17020532 ]
  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:12861354 ]
  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:15684812 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 31, 2016 02:14