Beclomethasone propionate

The ventilated and perfused human lung lobe was used as described by Linder and co-workers [74], A twofold difference in the appearance of drug and metabolites in the perfusate was found for the two formulations. Small fractions of the applied dose of BDP were immediately detectable in the perfusate and the amount of the major metabolite, beclomethasone-17-propionate (17-BMP), increased over the experimental period. These observations were similar to the clinical observations that BDP is detected rapidly in the plasma after inhalation and that the appearance of the active metabolite 17-BMP occurs rapidly. The kinetic differences between the formulations were explained on the basis of particle size effects with the conclusion that the discriminatory value of this system to examine the lung pharmacokinetics of inhaled medicines in the absence of systemic effects such as hepatic metabolism was apparent. 

Metabolites (Activity) beclomethasone 17-mono-propionate (active), free beclome-thasone (very weak anti-inflammatory effects) 16 -hydroxy-prednisolone and 6 -hydroxy-budesonide (< 1 % of parent) 67-OH (low corticosteroid potency) ... 

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. 

F. Chanoine, C. Grenot, P. Heidmann, and J. L. Junien, Pharmacokinetics of butixo-cort 21-propionate, budesonide, and beclomethasone dipropionate in the rat after intratracheal, intravenous, and oral treatments, Drug Metab. Dispos. 79 546 (1991). 

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. 

Beclomethasone Dipropionate. Beclomethasonc di-propionate (Beclovcnt. Beconase, Vanccril, Vanccna.se) (BDP) is rapidly converted in the lungs to beclomethasone... 

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