Glucocorticoids fluticason propionate

Callejas, S.L. Biddlecombe, R.A. Jones, A.E. Joyce, K.B. Pereira, A.I. Pleasance, S. Determination of the glucocorticoid fluticasone propionate in plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry, J.Chromatogr.B, 1998, 718, 243-250. 

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. 

A 32-month-old girl developed hypoglycemic seizures (61). She had been given fluticasone propionate 440-880 micrograms/day and up to 5 months before the incident oral glucocorticoids. 

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. 

Monitoring children using inhaled glucocorticoids has been discussed (1). Children using low to moderate doses of inhaled glucocorticoids (up to 200 micrograms of fluticasone propionate or budesonide) do not require routine... 

Fluticasone propionate is a novel glucocorticoid under investigating for the treatment of astluna and rhinitis. Li et al. [15, 27] developed a quantitative method for the analysis of budesonide and fluticasone propionate in human plasma to support a clinical study. The analytes were extracted from plasma by C,8-SPE. Budesonide was acetylated to form the 21-acetyl derivatives [7]. The compounds are analysed using LC-MS-MS in positive-ion APCl mode. Linearity was achieved over 0.05-10 ng/ml for budesonide and 0.02-4 ng/ml for fluticasone propionate. Intra- and inter-day precision was better than 14.3%. Plasma concentration profiles have been acquired. 

There are three aerosolized corticosteroid preparatioias available in MDI formulation for administration to horses via the Equine AeroMask beclometasone dipropionate, fluticasone propionate and flunisolide (Table 16.2). In terms of the relative potency, fluticasone is more potent than beclometasone, which is more potent than flunisolide, which is equipotent to triamcinolone. Using dexamethasone as the standard (1.0), the relative glucocorticoid receptor affinity of the common corticosteroids is flunisolide 1.9, triamcinolone 2.0, beclometasone (active metabolite) 13.5 and fluticasone propionate 22.0 (Barnes et al 1998). The pulmonary residence time of the aerosolized corticosteroids is determined by the lipophilicity of each drug. Flunisolide has intermediate water solubility (lOmg/ml), simitar to... 

Flogger P, Rohdewald P (1994). Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids. 59 597-602. 

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