Loteprednol etabonate

C23H30O7 133991-63-6) see Loteprednol etabonate (3p,16p,17a,18p,20a)-18-[[3-I4-t(ethoxycarbonyl)oxy]-3-methoxyphenyl)-l-oxo-2-propenyl]oxy]-ll,17-dimeth-oxyyohimban-16-carboxylic acid methyl ester (C3ftH42N20(o 49806-34-0) see Rescimetol AT-(l-ethoxycarbonyI-3-phenylpropyl)-L-alanine (C,, H 3N04) see Quinapril hydrochloride A7-[l(5)-ethoxycarbonyl-3-phenylpropyl]-L-alanine (C,gH2 N04 82717-962) see Imidapril Moexipril Quinapril hydrochloride Spirapril Trandolapril A -[l(5)-ethoxycarbonyl-3-phenylpropyl]-L-aIanine benzo-thiazol-2-yIthio ester... 

C21H2SO5 50-24-8) see Loteprednol etabonate Prednicarbate Prednimustine Prednisolamate, Prednisolone sodium phosphate Prednisolone sodium succinate Prednisolone sodium sulfobenzoate Prednisolone steaglate Prednisolone tebutate Prednisolone 21-trimethylacetate ... 

Recent results suggest a promising application of soft drugs in the field of topical corticosteroids (e.g., loteprednol etabonate [142]) and calcium antagonists (e.g., clevipidine [143]). 

N. Bodor, T. Loftsson, W. M. Wu, Metabolism, Distribution, and Transdermal Permeation of a Soft Corticosteroid, Loteprednol Etabonate , Pharm. Res. 1992, 9, 1275-1278 N. Bodor, W. M. Wu, T. Murakami, S. Engel, Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats , Pharm. Res. 1995, 72, 875-879. 

LOTEPREDNOL ETABONATE Shake well before using. 

Loteprednol etabonate (ophthalmic sol) Corticosteroid, ophthalmic anti-inflammatory... 

Glucocorticoids that have been used for local ophthalmic treatment include medrysone, fluorometholone, tetrahy-droxytriamcinolone, and clobetasone. Loteprednol etabo-nate 0.5% increases intraocular pressure less than dexamethasone. Studies on animal models of uveitis and two randomized double-masked trials showed that loteprednol etabonate 0.5% was less potent than dexamethasone, prednisolone acetate 1%, or fluorometholone, which may partly explain the improved toxicity profile of loteprednol etabonate (429). 

Figure 2 Design and metabolism of soft corticosteroids (1) based on the inactive metabolite approach. The acid metabolites (2, 3) are inactive, but suitable substitution at the 17a-hydroxy and 17(5-carboxy functions (R h R2) can restore corticosteroid activity and also allow facile one-step deactivation. Loteprednol etabonate (4), a soft steroid, is an active anti-inflammatory compound that lacks the IOP-elevating side effect of the other steroids used ophthalmically.

Selection of the final candidate for development was based on various properties. In addition to the therapeutic index, availability, synthesis, and softness (the rate and easiness of metabolic deactivation) also had to be considered. Loteprednol etabonate (4, chloromethyl 17a-ethoxycarbonyloxy-l lp-hydroxy-3-oxoandrosta-1,4-diene, 17P-carboxylate 1 A1, R = CH2C1, R2 = COOC2H5,... 

Table 1 Comparison of Loteprednol Etabonate with Other Steroids...

Figure 4 Change in IOP of normotensive rabbits treated with 0.1% dexamethasone (Dex), 0.1% loteprednol etabonate (LE), and vehicle (50% w/w 2-hydroxypropyl- 3-cyclo-dextrin water solution). Twelve rabbits were investigated in crossover experiments drugs were administered in one eye (100 pL) every hour during the 8-h periods marked on the graph. (Data from Ref. 43 represent mean SE both for treated (T) and control (C) eyes.)...

Proving effective reversed targeting, which results from the soft nature of this steroid, systemic levels or effects cannot be detected even after chronic ocular administration [57], Plasma levels of loteprednol etabonate and its primary metabolite (PJ-91) were less than the 1 ng/L detection limit in 10 healthy volunteers who received the drug in both eyes eight times daily for 2 days and four times daily for a further 41 days [57], In addition to its already approved uses, loteprednol etabonate is also being developed for the treatment of colitis, atopic dermatitis, and asthma based on promising results from animal studies [47, 48],... 

P. Druzgala, G. Hochhaus, and N. Bodor, Soft drugs. 10. Blanching activity and receptor binding affinity of a new type of glucocorticoid loteprednol etabonate, J. Steroid Biochem. 38 149 (1991). 

P. Druzgala, W.-M. Wu, and N. Bodor, Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes, Curr. Eye Res. 10 933 (1991). 

N. Bodor, N. Bodor, and W.-M. Wu, A comparison of intraocular pressure elevating activity of loteprednol etabonate and dexamethasone in rabbits, Curr. Eye Res. 11 525 (1992). 

N. Bodor, T. Loftsson, and W.-M. Wu, Metabolism, distribution, and transdermal permeability of a soft corticosteroid, loteprednol etabonate, Pharm. Res. 9 1275 (1992). 

G. Hochhaus, L.-S. Chen, A. Ratka, P. Druzgala, J. Howes, N. Bodor, and H. De-rendorf, Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs, J. Pharm. Sci. 81 1210 (1992). 

T. Loftsson and N. Bodor, The pharmacokinetics and transdermal delivery of loteprednol etabonate and related soft steroids, Adv. Drug Del. Rev. 14 293 (1994). 

Horwitz, Safety and efficacy of loteprednol etabonate for treatment of papillae in contact lens-associated giant papillary conjunctivitis, Curr. Eye Res. 12 313 (1993). 

J. D. Bartlett, B. Horwitz, R. Laibovitz, and J. F. Howes, Intraocular pressure response to loteprednol etabonate in known steroid responders, J. Ocul. Pharmacol. 9 157 (1993). 

J. F. Howes, H. Baru, M. Vered, and R. Neumann, Loteprednol etabonate comparison with other steroids in two models of intraocular inflammation, J. Ocul. Pharmacol. 10 289 (1994). 

P. Asbell and J. Howes, A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis, CLAO J. 23 31 (1997). 

S. J. Dell, G. M. Lowry, J. A. Northcutt, J. Howes, G. D. Novack, and K. Hart, A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis, J. Allergy Clin. Immunol. 102 251 (1998). 

J. Howes and G. D. Novack, Failure to detect systemic levels and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration, J. Ocul. Pharmacol. Ther 14 153 (1998). 

G. D. Novack, J. Howes, R. S. Crockett, and M. B. Sherwood, Change in intraocular pressure during long-term use of loteprednol etabonate, J. Glaucoma 7 266 (1998). 

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