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| Clinical data | |
|---|---|
| Trade names | Lotemax |
| Other names | 11β,17α,Dihydroxy-21-oxa-21-chloromethylpregna-1,4-diene-3,20-dione 17α-ethylcarbonate |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Routes of administration | Eye drops |
| Drug class | Corticosteroid;glucocorticoid |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | None |
| Protein binding | 95% |
| Metabolism | Ester hydrolysis |
| Metabolites | Δ1-cortienic acid and its etabonate |
| Onset of action | ≤2 hrs (allergic conjunctivitis) |
| Eliminationhalf-life | 2.8 hrs |
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| CAS Number | |
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| IUPHAR/BPS | |
| DrugBank |
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| ChemSpider |
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| UNII | |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.167.120 |
| Chemical and physical data | |
| Formula | C24H31ClO7 |
| Molar mass | 466.96 g·mol−1 |
| 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 (synthesized as theesterloteprednol etabonate) is a topicalcorticosteroid used to treat inflammations of the eye. It is marketed byBausch and Lomb asLotemax[2] andLoterex.
It was patented in 1980 and approved for medical use in 1998.[3] It is available as ageneric medication.[4]
Applications for this drug include the reduction ofinflammation after eye surgery,[2] seasonalallergic conjunctivitis,uveitis,[5] and chronic forms ofkeratitis - such asadenoviral,Thygeson's keratitis,vernal keratoconjunctivitis,pingueculitis, giant papillary conjunctivitis, andepiscleritis.[6]
Contraindications: As corticosteroids areimmunosuppressive, loteprednol is contraindicated in patients withviral,fungal ormycobacterial infections of the eye.[2][5][7]
The most commonadverse effects in patients being treated with the gel formulation are anterior chamber inflammation (in 5% of people), eye pain (2%), and foreign body sensation (2%).[8]
Because long term use (more than 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.[2]
Corticosteroids mediate their anti-inflammatory effects mainly through the modulation of the cytosolic glucocorticoid receptor (GR) at the genomic level. Preclinical studies demonstrated that loteprednol etabonate is highly lipophilic and has strong binding affinity to glucocorticoid receptors. After it binds to the GR in the cytoplasm, the activated corticosteroid-GR complex migrates to the nucleus, where it upregulates the expression of anti-inflammatory proteins and represses the expression of proinflammatory proteins. Corticosteroids inhibit inflammatory cytokines, chemokines, adhesion molecules, and other inflammatory mediators. They also reduce synthesis of histamine, stabilize cell membranes, and inhibit degranulation of mast cells. Recent work suggests that the activated corticosteroid-GR complex also elicits nongenomic effects, particularly the inhibition of vasodilation, vascular permeability, and migration of leukocytes.[9][10][11]
Neither loteprednol etabonate nor its inactivemetabolites Δ1-cortienic acid and Δ1-cortienic acidetabonate are detectable in the bloodstream, even afteroral administration. A study with patients receiving loteprednol eye drops over 42 days showed noadrenal suppression, which would be a sign of the drug reaching the bloodstream to a clinically relevant extent.[2]
Steroid receptor affinity was 4.3 times that ofdexamethasone in animal studies.[2]
Loteprednol etabonate was developed usingretrometabolic 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 ofhydrocortisone.[2][7][12]
Loteprednol etabonate is an ester of loteprednol withetabonate (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,[7] therefore it is formulated for ophthalmic use as either an ointment, a gel, or a suspension.[13]
Loteprednol is acorticosteroid. Theketone side chain of classical corticosteroids such ashydrocortisone is replaced by a cleavable ester, which accounts for the rapid inactivation.[14] (This is not the same as the etabonate ester.)
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