Peringatan Keamanan

The most common adverse drug reactions reported during clinical trials for the medication were eye pain and posterior capsular opacification, both of which may also be the consequence of the very surgical procedures performed on the eye(s) FDA Label.

The agent is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug FDA Label.

The medication is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child to the agent FDA Label.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay FDA Label.

Overdose is not expected to be likely to occur after ocular administration F1467.

Loteprednol etabonate

DB14596

small molecule approved

Deskripsi

Loteprednol Etabonate (LE) is a topical corticoid anti-inflammatory. It is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitides. As a nasal spray, it can be used for the treatment and management of seasonal allergic rhinitis.

Most prescription LE products, however, tend to be indicated for the treatment of post-operative inflammation and pain following ocular surgery FDA Label. A number of such new formulations that have been approved include Kala Pharmaceutical's Inveltys - the first twice-daily (BID) ocular corticosteroid approved for this indication, designed specifically to enhance patient compliance and simplified dosing compared to all other similar ocular steroids that are dosed four times daily L4545.

Moreover, LE was purposefully engineered to be a 'soft drug', one that is designed to be active locally at the site of administration and then rapidly metabolized to inactive components after eliciting its actions at the desired location, thereby subsequently minimizing the chance for adverse effects A38693.

Struktur Molekul 2D

Berat 466.96
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life of loteprednol etabonate as determined when administered intravenously at a dose of 5 mg/kg in the dog animal model is 2.8 hours [A38682].
Volume Distribusi The only data available regarding the volume of distribution of loteprednol etabonate (LE) is the volume of distribution the agent demonstrated when administered to dogs - a value of 3.7 L/kg [A38682]. It has been shown, however, that the topical ocular administration of LE distributes preferentially into the cellular components of blood [F1467].
Klirens (Clearance) Loteprednol etabonate was slowly hydrolyzed in liver at clearance rates of 0.21 +/- 0.04 and 2.41 +/- 0.13 ml/h/kg in the liver and plasma, respectively [A38681].

Absorpsi

Loteprednol etabonate (LE) demonstrates good ocular permeation properties as it is lipid soluble, allowing the agent to penetrate into cells with relative ease FDA Label, A1312. Results from the ocular administration of loteprednol in normal, healthy volunteers have shown that there are low or undetectable concentrations of either unchanged material or its metabolite L4539. Following twice-daily unilateral topical ocular dosing of LE for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all time points FDA Label. These finds suggest that limited, if any, systemic absorption of LE occurs L4539.

Metabolisme

Loteprednol etabonate (LE) is readily and extensively metabolized to two inactive metabolites, PJ-90 (?1-cortienic acid) and PJ-91 (?1-cortienic acid etabonate) FDA Label, F1467. Metabolism occurs locally in ocular tissues, and to the extent that loteprednol etabonate reaches the systemic circulation, likely the liver and other tissues into which it distributes F1467. In particular, studies have demonstrated that LE (chloromethyl 17alpha-ethoxycarbonyloxy-11beta-hydroxy-3-oxoandrosta-1,4-diene) is rapidly hydrolyzed at the location of its 17beta-chloromethyl ester function by paraoxonase 1 in human plasma at the site of administration at the level of the affected eye tissue to the 17beta-carboxylate PJ-91 metabolite and PJ-90 metabolite A38681, A38693. Both metabolites are considered inactive FDA Label, A38693, A38693.

Rute Eliminasi

Following systemic administration to rats, loteprednol etabonate is eliminated primarily via the biliary/faecal route, with most of the dose eliminated in the form of the metabolite, PJ-90 F1467.

Interaksi Obat

0 Data
Tidak ada data.

Target Protein

Steroid hormone receptor ERR1 ESRRA
Steroid hormone receptor ERR2 ESRRB
Estrogen-related receptor gamma ESRRG
Glucocorticoid receptor NR3C1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 18245274
    Pavesio CE, Decory HH: Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9. doi: 10.1136/bjo.2007.132621. Epub 2008 Feb 1.
  • PMID: 28017774
    Samir A, Bodor N, Imai T: Identification of esterase involved in the metabolism of two corticosteroid soft drugs. Biochem Pharmacol. 2017 Mar 1;127:82-89. doi: 10.1016/j.bcp.2016.12.010. Epub 2016 Dec 22.
  • PMID: 1491342
    Hochhaus G, Chen LS, Ratka A, Druzgala P, Howes J, Bodor N, Derendorf H: Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs. J Pharm Sci. 1992 Dec;81(12):1210-5.
  • PMID: 1959381
    Druzgala P, Wu WM, Bodor N: Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991 Oct;10(10):933-7.

Contoh Produk & Brand

Produk: 30 • International brands: 2
Produk
  • Alrex
    Suspension / drops • 2 mg/1mL • Ophthalmic • US • Approved
  • Alrex
    Suspension / drops • 2 mg/1mL • Ophthalmic • US • Approved
  • Alrex
    Suspension / drops • 2 mg/1mL • Ophthalmic • US • Approved
  • Alrex
    Suspension • 0.2 % w/v • Ophthalmic • Canada • Approved
  • Eysuvis
    Suspension / drops • 2.5 mg/1mL • Ophthalmic • US • Approved
  • Inveltys
    Suspension • 10 mg/1mL • Topical • US • Approved
  • Lotemax
    Suspension / drops • 5 mg/1mL • Ophthalmic • US • Approved
  • Lotemax
    Gel • 5 mg/1g • Ophthalmic • US • Approved
Menampilkan 8 dari 30 produk.
International Brands
  • Eysuvis
  • Loteflam — Cipla Pharmaceuticals Limited

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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