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
Synonyms
  • Loteprednol
  • Loteprednolum
External IDs
CDDD 5604 / HGP 1 / P 5604
Product Ingredients
IngredientUNIICASInChI Key
Loteprednol etabonateYEH1EZ96K682034-46-6DMKSVUSAATWOCU-HROMYWEYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlrexSuspension / drops2 mg/mLOphthalmicStat Rx USA1998-03-09Not applicableUs
AlrexSuspension / drops2 mg/mLOphthalmicBauch & Lomb Incorporated1998-03-09Not applicableUs
AlrexSuspension0.2 %OphthalmicBausch & Lomb Inc2009-06-24Not applicableCanada
AlrexSuspension / drops2 mg/mLOphthalmicPhysicians Total Care, Inc.2002-10-17Not applicableUs
LotemaxGel5 mg/gOphthalmicBauch & Lomb Incorporated2012-10-12Not applicableUs
LotemaxSuspension / drops5 mg/mLOphthalmicPhysicians Total Care, Inc.2002-10-17Not applicableUs
LotemaxOintment5 mg/gOphthalmicBauch & Lomb Incorporated2011-04-15Not applicableUs
LotemaxSuspension / drops5 mg/mLOphthalmicBauch & Lomb Incorporated1998-03-09Not applicableUs
LotemaxSuspension0.5 %OphthalmicBausch & Lomb Inc2009-06-24Not applicableCanada
Lotemax GelGel0.5 %OphthalmicBausch & Lomb Inc2015-06-25Not applicableCanada
International/Other Brands
Loteflam (Cipla Pharmaceuticals Limited)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ZyletLoteprednol etabonate (5 mg/mL) + Tobramycin (3 mg/mL)Suspension / dropsOphthalmicBauch & Lomb Incorporated2004-12-14Not applicableUs
Categories
UNII
Z8CBU6KR16
CAS number
129260-79-3
Weight
Average: 394.889
Monoisotopic: 394.154701681
Chemical Formula
C21H27ClO5
InChI Key
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

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.

Structured Indications
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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB15011
KEGG Drug
D01689
PubChem Compound
9865442
PubChem Substance
46504713
ChemSpider
8041134
ChEBI
50848
Therapeutic Targets Database
DAP001045
PharmGKB
PA164764569
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Loteprednol
ATC Codes
S01BA14 — Loteprednol
AHFS Codes
  • 52:08.08 — Corticosteroids
FDA label
Download (1.1 MB)
MSDS
Download (57.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailablePharmacokinetics1
1CompletedSupportive CareOcular Pain1
1CompletedTreatmentHealthy Volunteers1
2CompletedPreventionConjunctivitis, Seasonal Allergic1
2CompletedTreatmentDry Eye Syndromes / Keratoconjunctivitis Sicca1
2CompletedTreatmentEye Dryness1
2CompletedTreatmentKeratoconjunctivitis Sicca1
2CompletedTreatmentBacterial blepharitis1
3Active Not RecruitingTreatmentCataracts1
3CompletedTreatmentCataracts / Inflammatory Reaction / Pain2
3CompletedTreatmentConjunctivitis, Seasonal Allergic1
3CompletedTreatmentBacterial blepharitis / Conjunctivitis / Corneal Inflammation1
3CompletedTreatmentInflammatory Reaction / Pain2
3CompletedTreatmentOcular Infections, Irritations and Inflammations1
3CompletedTreatmentPost Surgical Ocular Inflammation and Pain1
3CompletedTreatmentOcular inflammatory conditions2
3RecruitingTreatmentDry Eye Syndromes / Keratoconjunctivitis Sicca2
4Active Not RecruitingTreatmentConjunctivitis, Giant Papillary / Conjunctivitis, Seasonal Allergic / Inflammatory Reaction1
4Active Not RecruitingTreatmentMeibomian Gland Dysfunction (MGD) / Posterior Blepharitis1
4CompletedPreventionCorneal Edema / Fuchs' Dystrophy1
4CompletedTreatmentBlepharokeratoconjunctivitis1
4CompletedTreatmentCataract Extraction1
4CompletedTreatmentChalazion / Hordeolum1
4CompletedTreatmentConjunctivitis1
4CompletedTreatmentConjunctivitis, Seasonal Allergic2
4CompletedTreatmentDry Eye Syndrome (DES)1
4CompletedTreatmentDry Eye Syndrome (DES) / Keratoconjunctivitis Sicca1
4CompletedTreatmentEpithelial Defect After Phototherapeutic Keratectomy1
4CompletedTreatmentInflammatory Reaction1
4CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
4Not Yet RecruitingTreatmentMust be PRK Candidate1
4Unknown StatusPreventionCataract operation / Pseudophakia1
4Unknown StatusTreatmentContact Lenses Dryness1
4WithdrawnTreatmentDry Eye Syndrome (DES)1
Not AvailableCompletedNot AvailableOcular Hypertension1
Not AvailableCompletedPreventionEye Dryness1
Not AvailableCompletedTreatmentDiabetic Macular Edema (DME) / Retinal Vein Occlusions(RVO)1
Not AvailableUnknown StatusNot AvailableInflammatory Reaction / Pseudophakia1
Not AvailableUnknown StatusTreatmentDry Eye Syndrome (DES)1
Not AvailableUnknown StatusTreatmentEye Dryness1
Not AvailableUnknown StatusTreatmentPost-operative Healing Following Blepharoplasty and Ptosis Repair1

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
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5540930No1993-10-252013-10-25Us
US4996335No1995-03-092012-03-09Us
CA2174550No2002-10-012014-10-21Canada
US5800807No1997-01-292017-01-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)220-224 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Androstane steroids
Direct Parent
Androgens and derivatives
Alternative Parents
3-oxo delta-1,4-steroids / 17-hydroxysteroids / 11-beta-hydroxysteroids / Delta-1,4-steroids / Tertiary alcohols / Secondary alcohols / Cyclic ketones / Cyclic alcohols and derivatives / Carboxylic acid esters / Monocarboxylic acids and derivatives
show 4 more
Substituents
Androgen-skeleton / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 17-hydroxysteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Oxosteroid / Hydroxysteroid / Delta-1,4-steroid / Tertiary alcohol
show 18 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
organochlorine compound, 11beta-hydroxy steroid, 17alpha-hydroxy steroid, androstanoid, 3-oxo-Delta(1),Delta(4)-steroid, steroid acid ester (CHEBI:50848)

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 modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
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]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2017 19:26