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==Adverse effects==
==Adverse effects==
Common adverse effects include foreign body sensation in the eye, dry eye and [[epiphora (medicine)|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<ref name="AC" /><ref name="Drugs.com" /> (compared to 7% under [[prednisolone acetate]], an older anti-inflammatory agent which is prescribed after eye surgery, and 0.5% under [[placebo]]).<ref name="Dinnendahl" /> Loteprednol is also far less likely to cause elevated IOP compared to [[dexamethasone]].{{fact|date=October 2016}}
Common adverse effects include foreign body sensation in the eye, dry eye and [[epiphora (medicine)|epiphora]] (overflow of tears), [[chemosis]] (swelling of the [[conjunctiva]]), headache, and itching.


==Interactions==
==Interactions==
Line 103: Line 103:
==References==
==References==
{{reflist|refs=
{{reflist|refs=
<ref name="Drugs.com">Loteprednol {{Drugs.com|ppa|loteprednol}}.</ref>
<ref name="AC">{{cite book|title=Austria-Codex|editor=Haberfeld, H.|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref>
<ref name="AC">{{cite book|title=Austria-Codex|editor=Haberfeld, H.|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref>
<ref name="Dinnendahl">{{cite book|title=Arzneistoff-Profile|editor1=Dinnendahl, V.|editor2=Fricke, U.|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|date=2008|edition=22|volume=6|isbn=978-3-7741-9846-3|language=German}}</ref>
<ref name="Druzgala">{{cite journal |author1=Druzgala, P. |author2=Hochhaus, G. |author3=Bodor, N. | title = Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate | journal = J. Steroid Biochem. Mol. Biol. | date = 1991 | volume = 38 | issue = 2 | pages = 149–54 | doi = 10.1016/0960-0760(91)90120-T| pmid = 2004037 }}</ref>
<ref name="Druzgala">{{cite journal |author1=Druzgala, P. |author2=Hochhaus, G. |author3=Bodor, N. | title = Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate | journal = J. Steroid Biochem. Mol. Biol. | date = 1991 | volume = 38 | issue = 2 | pages = 149–54 | doi = 10.1016/0960-0760(91)90120-T| pmid = 2004037 }}</ref>
<ref name="Dekker">{{cite book|title=Inhaled Steroids in Asthma. Optimizing Effects in the Airways|year=2002|publisher=Marcel Dekker, New York|pages=541–564|author=Bodor, N.|chapter=Design and development of a soft corticosteroid, loteprednol etabonate|author2=Buchwald, P. |editor=Schleimer, R.P. |editor2=O'Byrne, P.M. |editor3=Szefler, S.J. |editor4=Brattsand, R.|work=Lung Biology in Health and Disease, Vol. 163}}</ref>
<ref name="Dekker">{{cite book|title=Inhaled Steroids in Asthma. Optimizing Effects in the Airways|year=2002|publisher=Marcel Dekker, New York|pages=541–564|author=Bodor, N.|chapter=Design and development of a soft corticosteroid, loteprednol etabonate|author2=Buchwald, P. |editor=Schleimer, R.P. |editor2=O'Byrne, P.M. |editor3=Szefler, S.J. |editor4=Brattsand, R.|work=Lung Biology in Health and Disease, Vol. 163}}</ref>

Revision as of 12:58, 4 October 2018

Loteprednol etabonate
Clinical data
Trade namesLotemax
Other names11β,17α,Dihydroxy-21-oxa-21-chloromethylpregna-1,4-diene-3,20-dione 17α-ethylcarbonate
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 (allergic conjunctivitis)
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 ☒N
  • Key:DMKSVUSAATWOCU-HROMYWEYSA-N ☒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] and Loterex.

Medical uses

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

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.

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

Main article: Glucocorticoid § 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]

  • Δ1-Cortienic acid, inactive metabolite of loteprednol
    Δ1-Cortienic acid, inactive metabolite of loteprednol
  • Cortienic acid, inactive metabolite of hydrocortisone
    Cortienic acid, inactive metabolite of hydrocortisone
  • Hydrocortisone, the "parent compound" of corticosteroids
    Hydrocortisone, the "parent compound" of corticosteroids

Chemistry

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

[6]

References

  1. ^ a b c d e f g Haberfeld, H., ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  2. ^ a b Cite error: The named reference Drugs.com was invoked but never defined (see the help page).
  3. ^ a b c Cite error: The named reference Dinnendahl was invoked but never defined (see the help page).
  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. ^ 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

  • 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.
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