ABSTRACT
AIM: Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults. METHODS: The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 µg/24 µg, adolescents and adults: 400 µg/24 µg) via DPI. RESULTS: The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001). CONCLUSION: The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.
Subject(s)
Anti-Asthmatic Agents/pharmacokinetics , Asthma/drug therapy , Beclomethasone/pharmacokinetics , Ethanolamines/pharmacokinetics , Administration, Inhalation , Adolescent , Adult , Age Factors , Aged , Analysis of Variance , Anti-Asthmatic Agents/administration & dosage , Asthma/physiopathology , Beclomethasone/administration & dosage , Body Size/physiology , Child , Cross-Over Studies , Ethanolamines/administration & dosage , Forced Expiratory Volume/drug effects , Formoterol Fumarate , Half-Life , Humans , Metered Dose Inhalers , Middle Aged , Young AdultABSTRACT
Absorption, emission, and excitation spectra for solid-state and solution of Tb(III), Dy(III), and Gd(III) complexes with the polypyridine ligand 6,6'-bis[bis(2-pyridylmethyl)-aminomethyl]-2,2'-bipyridine (C36H34N8) are presented. Measurements of excited-state lifetimes and quantum yields in various solvents at room temperature and 77 K are also reported and used to characterize the excited-state energetics of this system. Special attention is given to the characterization of metal-to-ligand energy transfer efficiency and mechanisms. The measurement of circularly polarized luminescence (CPL) from the solution of the Dy(III) complex following circularly polarized excitation confirms the chiral structure of the complexes under study. No CPL is present in the luminescence from the Eu(III) or Tb(III) complex because of efficient racemization. The variation of the magnitude of the CPL as a function of temperature from an aqueous solution of DyL is used for the first time to characterize the solution equilibria between different chiral species.
Subject(s)
2,2'-Dipyridyl/analogs & derivatives , Lanthanoid Series Elements/chemistry , Pyridines/chemistry , 2,2'-Dipyridyl/chemistry , Chemistry, Physical/methods , Electrons , Europium/chemistry , Ligands , Luminescence , Models, Chemical , Stereoisomerism , Temperature , Terbium/chemistry , Water/chemistryABSTRACT
The title compound, C6H9N2+*C6H4NO2-, has been formed by oxidative degradation of neat bis(2-pyridylmethyl)amine. Hydrogen bonds link the ions into infinite chains along the a axis.
