Loteprednol

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Loteprednol etabonate
Loteprednol etabonate.svg
Clinical data
Trade names Lotemax
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Eye drops
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability None
Protein binding 95%
Metabolism Ester hydrolysis
Metabolites Δ1-cortienic acid and its etabonate
Onset of action ≤2 hrs (allergic conjunctivitis)
Biological half-life 2.8 hrs
Identifiers
Synonyms 11β,17α,Dihydroxy-21-oxa-21-chloromethylpregna-1,4-diene-3,20-dione 17α-ethylcarbonate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.167.120
Chemical and physical data
Formula C24H31ClO7
Molar mass 466.951 g/mol
3D model (Jmol)
Melting point 220.5 to 223.5 °C (428.9 to 434.3 °F)
Solubility in water 0.0005 mg/mL (20 °C)
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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[1] and Loterex.

Medical uses[edit]

Applications for this drug include the reduction of inflammation after eye surgery,[1] seasonal allergic conjunctivitis, uveitis,[2] as well as chronic forms of keratitis (e.g. adenoviral and Thygeson's keratitis), vernal keratoconjunctivitis, pingueculitis, and episcleritis.[citation needed]

Contraindications[edit]

As corticosteroids are immunosuppressive, loteprednol is contraindicated in patients with viral, fungal or mycobacterial infections of the eye.[1][2][3]

Adverse effects[edit]

Common adverse effects include foreign body sensation in the eye, dry eye and epiphora (overflow of tears), chemosis (swelling of the conjunctiva), headache, and itching. Increased intraocular pressure (IOP), a side effect typical of corticosteroids, occurs in about 2% of patients[1][2] (compared to 7% under prednisolone acetate, an older anti-inflammatory agent which is prescribed after eye surgery, and 0.5% under placebo).[3] Loteprednol is also far less likely to cause elevated IOP compared to dexamethasone.[citation needed]

Interactions[edit]

The effect of drugs lowering intraocular pressure may be reduced. Loteprednol is not detectable in the bloodstream; so interactions with systemic drugs are highly unlikely.[1]

Pharmacology[edit]

Mechanism of action[edit]

Pharmacokinetics[edit]

Neither loteprednol etabonate nor its inactive metabolites Δ1-cortienic acid and Δ1-cortienic acid etabonate are detectable in the bloodstream, even after oral administration. A study with patients receiving loteprednol eye drops over 42 days showed no adrenal suppression, which would be a sign of the drug reaching the bloodstream to a clinically relevant extent.[1]

Steroid receptor affinity was 4.3 times that of dexamethasone in animal studies.[1]

Retrometabolic drug design[edit]

Loteprednol etabonate was developed using retrometabolic drug design. It is a so-called soft drug, meaning its structure was designed so that it is predictably metabolised to inactive substances. These metabolites, Δ1-cortienic acid and its etabonate, are derivatives of cortienic acid, itself an inactive metabolite of hydrocortisone.[1][3][4]

Chemistry[edit]

Loteprednol etabonate is an ester of loteprednol with etabonate (ethyl carbonate), with a melting point between 220.5 °C (428.9 °F) and 223.5 °C (434.3 °F). Its solubility in water is 1:2,000,000.[3] The ketone in the side chain of classical corticosteroids such as hydrocortisone is replaced by a cleavable ester, which accounts for the rapid inactivation.[5] (This is not the same as the etabonate ester.)

Chemical synthesis[edit]

Loteprednol.png

[6]

References[edit]

  1. ^ a b c d e f g h Haberfeld, H., ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 
  2. ^ a b c Loteprednol Professional Drug Facts.
  3. ^ a b c d Dinnendahl, V.; Fricke, U., eds. (2008). Arzneistoff-Profile (in German). 6 (22 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. 
  4. ^ Bodor, N.; Buchwald, P. (2002). "Design and development of a soft corticosteroid, loteprednol etabonate". In Schleimer, R.P.; O'Byrne, P.M.; Szefler, S.J.; Brattsand, R. Inhaled Steroids in Asthma. Optimizing Effects in the Airways. Lung Biology in Health and Disease, Vol. 163. Marcel Dekker, New York. pp. 541–564. 
  5. ^ Pavesio, C.E.; Decory, H.H. (2008). "Treatment of ocular inflammatory conditions with loteprednol etabonate". Br J Ophthalmol. 92 (4): 455–459. doi:10.1136/bjo.2007.132621. PMID 18245274. 
  6. ^ Druzgala, P.; Hochhaus, G.; Bodor, N. (1991). "Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate". J. Steroid Biochem. Mol. Biol. 38 (2): 149–54. doi:10.1016/0960-0760(91)90120-T. PMID 2004037. 

Further reading[edit]

  • Steward, R.; et al. (November 1998). "Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1". J Cataract Refract Surg. 24 (11): 1480–1489. PMID 9818338.