Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate. 2012

Amira S A Said, and Lindsay P Harding, and Henry Chrystyn
Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, UK.

OBJECTIVE Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHODS Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 µg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10,100 µg inhalations from a Qvar(®) Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 µg inhalations from a Clenil(®) pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone-17-monopropionate (17-BMP) and beclometasone (BOH) were measured. RESULTS No BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSIONS The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002606 Charcoal An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed) Activated Charcoal,Actidose,Actidose-Aqua,Adsorba,Carbomix,Charbon,CharcoAid,CharcoCaps,Charcodote,Formocarbine,Insta-Char,Kohle-Compretten,Kohle-Hevert,Kohle-Pulvis,Kohle-Tabletten Boxo-Pharm,Liqui-Char,Norit,Ultracarbon,Charcoal, Activated
D005260 Female Females
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001507 Beclomethasone An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of ASTHMA. Beclomethasone Dipropionate,AeroBec Forte,Aerobec,Aldecin,Apo-Beclomethasone,Ascocortonyl,Asmabec Clickhaler,Beclamet,Beclazone,Beclazone Easy Breathe,Beclo AZU,Beclo Asma,Beclocort,Becloforte,Beclomet,Beclometasone,Beclorhinol,Becloturmant,Beclovent,Becodisk,Becodisks,Beconase,Beconase AQ,Becotide,Bemedrex Easyhaler,Bronchocort,Ecobec,Filair,Filair Forte,Junik,Nasobec Aqueous,Prolair,Propaderm,Qvar,Respocort,Sanasthmax,Sanasthmyl,Vancenase,Vanceril,Ventolair,Viarin,Dipropionate, Beclomethasone

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