Fluticasone dipropionate

PET techniques offer the important advantage in that the drug under study can be firmly labeled with the appropriate positron emitting isotope, usually nC or 1SF. Thus, deposition reflects the pharmaceutical itself, without interference from free isotope. Fluticasone dipropionate, triamcinolone acetonide, and zanamivir have all been labeled and their dose and distribution in the respiratory tract and/or the nasal cavity assessed with PET [48,50,123],... 

A 2-year-old boy had used inhaled fluticasone-dipropionate 100 micrograms/day for frequent episodes of asthma and had also intermittently received prednisone suppositories (Recto-delt ) for acute bronchopulmonary obstruction with no adverse outcomes. During a bout of severe bronchospasm he was given intravenous prednisolone-21-hydrogen succinate 50 mg (Solu-Decortin ) and within a few... 

Bernal, J.L. Del Nozal, M. J. Martin, M.T. Diez-Masa, J.C. Cifuentes, A. Quantitation of active ingredients and excipients in nasal sprays by high-performance liquid chromatography, capUlsiry electrophoresis and UV spectroscopy, J.ChromatogrA., 1998, 823, 423-431. [beclomethasone dipropionate fluticasone dipropionate beclomethasone fluticasone benzalkonium benzalkonium chloride phenylethyl... 

C3H5CIO 79-03-8) see Betamethasone butyrate propionate Betamethasone dipropionate Docarpamine Erythromycin estolate Erythromycin monopropionate mercaptosuccinate Flavoxate Fluticasone propionate Naproxen Prednicarbate Quinethazone 2-propionyloxybenzoic acid (Ci H,o04 6328-44-5) see Flavoxate... 

Examples of group I, i.e. weak or low efficacy topical steroids, are hydrocortisone acetate in various concentrations, methylprednisolone 1.0% and prednisolone 0.5%. Group II, the moderately potent steroids, includes alclometasone dipropionate 0.05%, hydrocortisone butyrate 0.1%, triamcinolone acetonide 0.025% and fluocinolone ace-tonide 0.01%. Group III, the potent steroids, contains among others betamethasone valerate 0.1%, betamethasone dipropionate 0.05%, budesonide 0.025%, desoximetasone 0.05%, fluticasone propionate 0.05%, amcinonide 0.1%, fluocinonide 0.05% and mometasone furoate 0.1%. Group IV comprises the very potent agents such as clobetasol propionate 0.05% and halobetasol propionate 0.05%. 

The corticosteroids are effective in most children and adults with asthma. They are beneficial for the treatment of both acute and chronic aspects of the disease. Inhaled corticosteroids, including triamcinolone ace-tonide (Azmflcort),beclomethasone dipropionate (Beclo-vent, Vancerit), flunisolide AeroBid), and fluticasone (Flovent), are indicated for maintenance treatment of asthma as prophylactic therapy. Inhaled corticosteroids are not effective for relief of acute episodes of severe bronchospasm. Systemic corticosteroids, including prednisone and prednisolone, are used for the short-term treatment of asthma exacerbations that do not respond to (32-adrenoceptor agonists and aerosol corticosteroids. Systemic corticosteroids, along with other treatments, are also used to control status asthmaticus. Because of the side effects produced by systemically administered corticosteroids, they should not be used for maintenance therapy unless all other treatment options have been exhausted. 

Corticosteroids beclomethasone dipropionate budesonide fluticasone propionate... 

The first inhaled glucocorticoid, beclomethasone dipropionate, revolutionized asthma therapy, when it was found that topical delivery to the lung resulted in reduced systemic side-effects (adrenal suppression, oseteoporosis and growth inhibition) typically seen with oral steroid treatments. Interestingly, a further reduction in systemic exposure was achieved with the introduction of fluticasone propionate (1). The evolution of this drug stemmed from observations with the steroid 17-carboxylates that showed that these esters were active topically when esterified, while the parent acids were inactive. Thus it was realized that enzymatic hydrolysis of the ester would lead to systemic deactivation. SAR studies led to a series of carbothioates, which were very active in vivo when topically applied to rodents, but were inactive after oral administration. It was shown that fluticasone propionate (1) underwent first pass metabolism in the liver to the corresponding inactive 173-carboxylic acid (la) (Scheme 1). This observation was... 

Systemic availability of inhaled glucocorticoids can be reduced in two ways. First, by using esters that reduced local absorption in the case of beclomethasone the dipropionate is used. Secondly, by using glucocorticoids that are extensively metabolized in the liver after absorption from the gut, such as fluticasone and budesonide. These strategies can be combined fluticasone is given as the ester fluticasone propionate. 

Treatment with beclomethasone dipropionate 1500 micrograms/day for 6 weeks significantly reduced markers of bone formation (osteocalcin and PICP), whereas fluticasone propionate 750 micrograms/day had no effect. Neither drug affected biochemical markers of bone resorption. There was no significant change in bone density (SEDA-22,183). 

In a 12-month, multicenter comparison of fluticasone propionate 250-500 micrograms/day with beclomethasone dipropionate 500-1000 micrograms/day, the two drugs had an equal therapeutic effect. Fluticasone propionate treatment resulted in a higher bone mineral density (assessed at the hip) and higher serum osteocalcin concentrations. 

Niitsuma T, Okita M, Sakurai K, Morita S, Tsuyuguchi M, Matsumura Y, Hayashi T, Koshishi T, Oka K, Homma M. Adrenal function as assessed by low-dose adrenocortico-tropin hormone test before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate. J Asthma 2003 40 515-22. 

Gregson RK, Rao R, Murrills AJ, Taylor PA, Warner JO. Effect of inhaled corticosteroids on bone mineral density in childhood asthma comparison of fluticasone propionate with beclomethasone dipropionate. Osteoporos Int 1998 8(5) 418-22. 

Fitzgerald D, Van Asperen P, Mellis C, Honner M, Smith L, Ambler G. Fluticasone propionate 750 micro-grams/day versus beclomethasone dipropionate 1500 micrograms/day comparison of efficacy and adrenal function in paediatric asthma. Thorax 1998 53(8) 656-61. 

Hydrocortisone, prednisolone, betamethasone, betamethasone dipropionate, clobetasol butyrate, fluticasone propionate, clobetasone butyrate, betamethasone-17-valerate Hypersil Cl8, 3 pm Acetonitrile-2 mM phosphate, pH 7.8 (80 20) 270 mm x 50 pm i.d. 200 mm packed length... 

Fluticasone propionate, when administered topically, about ten-fold more active, whereas beclomethasone dipropionate is five-fold more active than fluoci-nolone acetonide using the vasoconstriction assay in man. 

Oral glucocorticoids such as dexamethasone and prednisolone are still used in patients with severe asthma, though these agents are associated with adverse systemic effects. Inhaled glucocorticoid therapy was introduced in 1972 with beclomethasone dipropionate, which dramatically reduced systemic effects. Fluticasone propionate (launched in 1993) is very efficiently inactivated in the liver, and exhibits low oral bioavailability, which in turn leads to a further reduction in systemic exposure. 

Hydrocortisone, prednisolone, betamethasone, betamethasone dipropionate, clobetasol butyrate, fluticasone propionate, clobetase butyrate, betamethasone-17-valerate... 

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