Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate

@article{Druzgala1991SoftDB,
  title={Soft drugs—10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate},
  author={Pascal Druzgala and Guenther Hochhaus and NICHOLAS S. Bodor},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  year={1991},
  volume={38},
  pages={149-154}
}
An improved synthesis of loteprednol etabonate (chloromethyl 17 alpha-ethoxycarbonyloxy-11 beta-hydroxy-3-oxoandrosta-1,4-diene 17 beta-carboxylate) was achieved. The design of the new type of glucocorticoid was based on the soft drug concept. The relative binding affinities of loteprednol and its putative metabolites (PJ90 and PJ91) to rat lung type II glucocorticoid receptor were determined in a competitive binding experiment with [3H]triamicinolone acetonide. The medium contained cortienic… 
Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs.
TLDR
Levels of intact drug and metabolites were highest in liver and kidney, whereas significantly lower levels were found in other investigated organs (lung, brain, heart).
Structural studies of loteprednol etabonate and other analogs of prednisolone using NMR techniques
TLDR
The stereochemical structure of loteprednol etabonate (chloromethyl 17 alpha-ethoxycarbonyloxy-11 beta-hydroxy-3-oxoandrosta-1,4-diene-17 beta-carboxylate, 1), a soft corticosteroid antiinflammatory drug, was proved to be analogous to prednisolone.
Budesonide and Ciclesonide: Effect of Tissue Binding on Pulmonary Receptor Binding
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The PK/PD model predicted lower receptor occupancy in the lung and the systemic tissues when a drug with pronounced binding was inhaled, including des-CIC, which was predicted to be lower than BUD.
Glucocorticoid receptor binding: A biphasic dependence on molecular size as revealed by the bilinear LinBiExp model
TLDR
A comprehensive quantitative analysis of relative RBA data obtained from more than a hundred active structures suggests binding is strongest for corticosteroids close to an ideal size that is large enough to provide as large nonspecific (van der Waals-type) interactions as possible, but is not too large to have difficulty fitting due to size-limitations at the binding site.
17β-carboxamide steroids--in vitro prediction of human skin permeability and retention using PAMPA technique.
TLDR
Based on the data, further structural modifications could be applied in order to increase retention without significant increase of permeability, which can positively affect potential local anti-inflammatory activity of these compounds.
Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate☆
TLDR
Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs, and the reduced potency suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities.
Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats
TLDR
The results indicate that LE absorbed systemically, after topical administration, can be rapidly transformed to the inactive metabolites, and eliminated from the body mainly through the bile and urine.
Pharmacokinetics and delta1-cortienic acid excretion after intravenous administration of prednisolone and loteprednol etabonate in rats.
TLDR
Detailed pharmacokinetic studies in rats were performed to compare the PK of prednisolone (PRN) and loteprednol etabonate (LE) as well as their common inactive metabolite delta1-cortienic acid (delta1-CA), and to investigate the excretion of delta 1-CA after PRN and LE administration.
An HPLC method to evaluate purity of a steroidal drug, loteprednol etabonate.
TLDR
A high-performance liquid chromatographic method was validated to evaluate purity of loteprednol etabonate and its four related substances, major process impurities and degradation products (PJ-90, PJ-91, LE-11-keto and LE-methyl ester) were well resolved using a phenyl-stationary phase under isocratic conditions.
Development of simultaneous quantification method of loteprednol etabonate (LE) and its acidic metabolites, and analysis of LE metabolism in rat
TLDR
Loteprednol etabonate is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions that disappears upon hydrolysis of either ester bond, producing the inactive metabolite, Δ1-cortienic acid (Δ1-CA).
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