|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
|Metabolites||Δ1-cortienic acid and its etabonate|
|Onset of action||≤2 hrs (allergic conjunctivitis)|
|Biological half-life||2.8 hrs|
|Chemical and physical data|
|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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Applications for this drug include the reduction of inflammation after eye surgery, seasonal allergic conjunctivitis, uveitis, as well as chronic forms of keratitis (e.g. adenoviral and Thygeson's keratitis), vernal keratoconjunctivitis, pingueculitis, and episcleritis.
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 (compared to 7% under prednisolone acetate, an older anti-inflammatory agent which is prescribed after eye surgery, and 0.5% under placebo). Loteprednol is also far less likely to cause elevated IOP compared to dexamethasone.
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.
Mechanism of action
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.
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.
Cortienic acid, inactive metabolite of hydrocortisone
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. The ketone in the side chain of classical corticosteroids such as hydrocortisone is replaced by a cleavable ester, which accounts for the rapid inactivation. (This is not the same as the etabonate ester.)
|This section needs expansion. You can help by adding to it. (June 2016)|
- Haberfeld, H., ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- Loteprednol Professional Drug Facts.
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- 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.