BECOTIDE EVOHALER Pressurised inhalation, solution Ref.[49849] Active ingredients: Beclometasone

Absorption

When administered via inhalation (via metered dose inhaler), systemic absorption of unchanged beclometasone dipropionate (BDP) occurs through the lungs with negligible oral absorption of the swallowed dose. There is extensive conversion of BDP to its active metabolite B-17-MP within the lung prior to absorption. The systemic absorption of B-17-MP arises from both lung deposition and oral absorption of the swallowed dose. The absolute bioavailability following inhalation is approximately 60% of the nominal dose forB-17-MP. BDP is absorbed rapidly with peak plasma concentrations first being observed (t_max) at 0.3h. B-17-MP appears more slowly with a t_max of 1 h. There is an approximately linear increase in systemic exposure with increasing inhaled dose. When administered orally the bioavailability of BDP is negligible but pre-systemic conversion to B-17-MP results in approximately 40% of the dose being absorbed as B-17-MP.

Metabolism

BDP is cleared very rapidly from the systemic circulation, by metabolism mediated via esterase enzymes that are found in most tissues. 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 the systemic exposure.

Distribution

The tissue distribution at steady-state for BDP is moderate (20 L) but more extensive for B-17-MP (424 L). Plasma protein binding is moderately high (87%).

Elimination

The elimination of BDP and B-17-MP is characterised by high plasma clearance (150 and 120 L/h) with corresponding terminal elimination half-lives of 0.5h and 2.7 h. 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. The renal clearance of BDP and its metabolites is negligible.

Preclinical safety studies indicate that beclometasone dipropionate shows negligible systemic toxicity when administered by the inhaled route.

The non-CFC propellant, Norflurane (HFA134a), has been shown to have no toxic effect at very high vapour concentrations, far in excess of those likely to be experienced by patients, in a wide range of animal species exposed daily for periods of two years.