Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Glaxo Wellcome UK Ltd., Trading as GlaxoSmithKline UK, 980 Great West Road, Brentford, Middlesex, TW8 9GS
Following topical administration beclometasone 17,21-dipropionate (BDP) produces potent anti-inflammatory and vasoconstrictor effects.
BDP is a pro-drug with weak corticosteroid receptor binding affinity. It is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate (B-17-MP), which has high topical anti-inflammatory activity.
Beclometasone dipropionate offers a preventative background treatment for hayfever when taken prior to allergen challenge. After which with regular use, BDP can continue to prevent allergy symptoms from reappearing.
Following intranasal administration of BDP in healthy males, the systemic absorption was assessed by measuring the plasma concentrations of its active metabolite B-17-MP, for which the absolute bioavailability following intranasal administration is 44% (95% CI 28%, 70%). After intranasal administration, <1% of the dose is absorbed by the nasal mucosa. The remainder after being cleared from the nose, either by drainage or mucocilary clearance, is available for absorption from the gastrointestinal tract. Plasma B-17-MP is almost entirely due to conversion of BDP absorbed from the swallowed dose.
Following oral administration of BDP in healthy males, the systemic absorption was also assessed by measuring the plasma concentrations of its active metabolite B-17-MP, for which the absolute bioavailability following oral administration is 41% (95% CI 27%, 62%).
Following an oral dose, B-17-MP is absorbed slowly with peak plasma levels reached 3-5 hours after dosing.
BDP is cleared very rapidly from the circulation and plasma concentrations are undetectable (<50pg/ml) following oral or intranasal dosing. There is rapid metabolism of the majority of the swallowed portion of BDP during its first passage through the liver. The main product of metabolism is the active metabolite (B-17-MP). Minor inactive metabolites, beclometasone-21-monopropionate (B-21-MP) and beclometasone (BOH), are also formed but these contribute little to systemic exposure.
The tissue distribution at steady-state for BDP is moderate (20l) but more extensive for B-17-MP (424l). Plasma protein binding of BDP is moderately high (87%).
The elimination of BDP and B-17-MP are characterised by high plasma clearance (150 and 120l/h) with corresponding terminal elimination half-lives of 0.5h and 2.7h. Following oral administration of tritiated BDP, approximately 60% of the dose was excreted in the faeces within 96 hours mainly as free and conjugated polar metabolites. Approximately 12% of the dose was excreted as free and conjugated polar metabolites in the urine.
No clinically relevant findings were observed in preclinical studies.
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