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Loteprednol

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Loteprednol etabonate
Clinical data
Trade namesLotemax
Other namesHGP 1
AHFS/Drugs.comMicromedex Detailed Consumer Information
Routes of
administration
Eye drops
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNone
Protein binding95%
MetabolismEster hydrolysis
MetabolitesΔ1-cortienic acid and its etabonate
Onset of action≤2 hrs
Elimination half-life2.8 hrs
Identifiers
  • Chloromethyl 17-ethoxycarbonyloxy-11-hydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17-carboxylate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.167.120 Edit this at Wikidata
Chemical and physical data
FormulaC24H31ClO7
Molar mass466.951 g/mol g·mol−1
3D model (JSmol)
Melting point220.5 to 223.5 °C (428.9 to 434.3 °F)
Solubility in water0.0005 mg/mL (20 °C)
  • CCOC(=O)O[C@@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)C=C[C@]34C)O)C)C(=O)OCCl
  • InChI=1S/C24H31ClO7/c1-4-30-21(29)32-24(20(28)31-13-25)10-8-17-16-6-5-14-11-15(26)7-9-22(14,2)19(16)18(27)12-23(17,24)3/h7,9,11,16-19,27H,4-6,8,10,12-13H2,1-3H3/t16-,17-,18-,19+,22-,23-,24-/m0/s1
  • Key:DMKSVUSAATWOCU-HROMYWEYSA-N
 ☒NcheckY (what is this?)  (verify)

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]

Medical uses

Ocular applications for this drug include the treatment of inflammation of the eye due to allergies, as well as chronic forms of keratitis (e.g. adenoviral and Thygeson's keratitis), vernal keratoconjunctivitis,[2] pingueculitis, and episcleritis.[citation needed] It is also used to reduce inflammation after eye surgery.[1]

Contraindications

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

Adverse effects

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, a side effect typical of corticosteroids, occurs in about 2% of patients[1][2] (compared to 7% under prednisolone acetate and 0.5% under placebo).[3]

Interactions

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

Mechanism of action

Pharmacokinetics

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

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]

Physical and chemical properties

Loteprednol etabonate melts between 220.5 and 223.5 °C. Its solubility in water is 1:2,000,000.[3] The drug is used as an ester of loteprednol with etabonate (ethyl carbonate).

Chemical synthesis

[5]

References

  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). Vol. 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. (eds.). Inhaled Steroids in Asthma. Optimizing Effects in the Airways. Marcel Dekker, New York. pp. 541–564. {{cite book}}: |work= ignored (help)
  5. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

  • Steward, R; et al. (November 1998). "Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation". J Cataract Surg. 24: 1480–1489.
  • Pavesio, CE; Decory, HH (2008). "Treatment of ocular inflammatory conditions with loteprednol etabonate". Br J Ophthalmol. 92 (4): 455–459. doi:10.1136/bjo.2007.132621. PMID 18245274.