Pharmacokinetics of butixocort 21-propionate, budesonide, and beclomethasone dipropionate in the rat after intratracheal, intravenous, and oral treatments.

Article

Author: Heidmann, P ; Grenot, C ; Chanoine, F ; Junien, J L

The disposition of butixocort 21-propionate (JO 1222) in the rat after intratracheal treatment with a pulmonary aerosol was compared to that of budesonide (BUD) and beclomethasone dipropionate (BDP) using tritium-labeled aerosols. Each aerosol canister delivered 50 micrograms of 3H-labeled steroid through an intratracheal catheter directly into the lung. Rats were sacrificed at different times after treatment. Lung and plasma concentrations of unchanged drug and active metabolites were measured by HPLC using a radioactivity detector. Tritium-labeled drugs (1.5 mg/kg) also were administered by the iv and oral routes for the purpose of comparing their systemic availability. The extent of biotransformation of all three steroids in the lung was very limited. JO 1222 was metabolized to the active compounds butixocort (JO 1717) and butixocort 21-methyl (JO 1605). BDP was transformed primarily to beclomethasone monopropionate (BMP); BUD was not metabolized in the lung. In contrast to these results, large differences were observed between plasma concentrations and systemic availability of the three drugs. BUD was rapidly absorbed from the lung, and its plasma elimination half-life was about 3 hr. BDP was hydrolyzed rapidly into its active metabolite BMP after intratracheal and iv treatments; BDP was not observed in plasma after oral treatment. Additionally, plasma concentrations of BMP were higher than those of BUD administered at the same doses. Assuming that BDP was transformed entirely into BMP, the oral bioavailability of BMP at 1.5 mg/kg was around 72%, while that of BUD was 15%. JO 1222 has a distinct pharmacokinetic profile due to the extensive metabolic clearance of both the unchanged drug and its active metabolites JO 1717 and JO 1605.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal of lipid mediators

Anti-inflammatory properties of tixocortol 17-butyrate,21-propionate (JO 1222), a novel, locally acting corticosteroid.

Article

Author: Grouhel, A ; Lelièvre, V ; Moodley, I ; Junien, J L

Tixocortol 17-butyrate,21-propionate (JO 1222) is a novel, locally acting, C-21 thioester-linked corticosteroid with significant activity in a number of models of inflammation. In models of acute inflammation, JO 1222 had an ED30 of 3 micrograms in carrageenan-induced oedema, an ED50 of 5 ng in croton oil-induced inflammation, and 4 micrograms and 2 micrograms/pleural cavity in carrageenin-induced pleurisy in the rat and mouse respectively. In a model of subchronic inflammation JO 1222 had an ED50 of 39 micrograms/pellet (cotton pellet-induced granuloma) and an ED50 of 13 ng in oxazolone-induced hypersensitivity. The overall relative potency was found to be beclomethasone DP greater than betamethasone DP = JO 1222 greater than hydrocortisone 17-butyrate,21-propionate greater than hydrocortisone acetate. In contrast to any of the other corticosteroids, including beclomethasone DP, JO 1222 did not have any marked systemic effects in any of the above models following oral or local administration. Furthermore, in contrast to other locally acting corticosteroids such as beclomethasone DP, JO 1222 had little or no effect on the thymus or body weight. These findings suggest that JO 1222 is a novel, potent, locally acting corticosteroid with little or no systemic effects and thus has therapeutical potential in diseases such as asthma, arthritis, ulcerative colitis and rhinitis.

100 Deals associated with Butixocort propionate

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KEGG	Wiki	ATC	Drug Bank
-	Butixocort propionate	-	-

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	-	3M Health Care, Inc.	-
Asthma	Phase 2	-	3M Health Care, Inc.	-
Asthma	Phase 2	-	Pfizer Inc.	-
Asthma	Phase 2	-	Pfizer Inc.	-
Rhinitis, Allergic	Phase 2	-	3M Health Care, Inc.	-
Rhinitis, Allergic	Phase 2	-	Pfizer Inc.	-
Rhinitis, Allergic	Phase 2	-	3M Health Care, Inc.	-
Rhinitis, Allergic	Phase 2	-	Pfizer Inc.	-

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