Loteprednol

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Loteprednol etabonate
Loteprednol etabonate.svg
Clinical data
Trade names Lotemax
Synonyms 11β,17α,Dihydroxy-21-oxa-21-chloromethylpregna-1,4-diene-3,20-dione 17α-ethylcarbonate
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)
Elimination half-life 2.8 hrs
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C24H31ClO7
Molar mass 466.951 g/mol
3D model (JSmol)
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]

The most common adverse effects in patients being treated with the gel formulation are anterior chamber inflammation (5%), eye pain (2%), and foreign body sensation (2%).[4]

Interactions[edit]

Because long term use (>10 days) can cause increased intraocular pressure, loteprednol may interfere with the treatment of glaucoma. Following ocular administration, the drug is very slowly absorbed into the blood, therefore the blood level is limited to an extremely small concentration, and interactions with drugs taken by mouth or through any route other than topical ophthalmic are very 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][5]

Chemistry[edit]

Loteprednol etabonate is an ester of loteprednol with etabonate (ethyl carbonate). The pure chemical compound has 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], therefore it is formulated for ophthalmic use as either an ointment, a gel, or a suspension.[6]

Loteprednol is a corticosteroid. The ketone side chain of classical corticosteroids such as hydrocortisone is replaced by a cleavable ester, which accounts for the rapid inactivation.[7] (This is not the same as the etabonate ester.)

Loteprednol

Chemical synthesis[edit]

Loteprednol.png [8]

References[edit]

  1. ^ a b c d e f g Haberfeld, H., ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  2. ^ a b Loteprednol Professional Drug Facts.
  3. ^ a b c 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. ^ "HIGHLIGHTS OF PRESCRIBING INFORMATION Lotemax" (PDF). 2012.
  5. ^ 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.
  6. ^ "Loteprednol (Professional Patient Advice)". Retrieved October 4, 2018.
  7. ^ 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.
  8. ^ 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. doi:10.1016/s0886-3350(98)80170-3. PMID 9818338.