Dry Powder Inhalation Exposures of the Endotracheally Intubated Rat Lung, Ex Vivo and In Vivo: The Pulmonary Pharmacokinetics of Fluticasone Furoate
| Autor: | Carl-Olof Sjöberg, Fernando Acevedo, Ewa Selg, Per Gerde, Åke Ryrfeldt, Pär Ewing |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.drug_class Pharmaceutical Science Pharmacology Models Biological Fluticasone propionate Dry powder inhalation Rats Sprague-Dawley Pharmacokinetics Adrenal Cortex Hormones In vivo Administration Inhalation Intubation Intratracheal medicine Animals Pharmacology (medical) Particle Size Lung Aerosols Inhalation Chemistry Reproducibility of Results Rats Androstadienes Perfusion medicine.anatomical_structure Corticosteroid Female Powders Ex vivo Half-Life medicine.drug |
| Zdroj: | Journal of Aerosol Medicine and Pulmonary Drug Delivery. 26:181-189 |
| ISSN: | 1941-2703 1941-2711 |
| Popis: | The isolated perfused rat lung (IPL) is a suitable model for studying lung-specific pharmacokinetics (PK) of inhaled drugs. So far, little has been known, however, whether the PK measured in the ex vivo organ corresponds to the PK measured in similarly exposed animals in vivo, in particular the endotracheally intubated rat (EIR). The purpose of the current research was to compare the PK of inhaled corticosteroid fluticasone furoate (FF) in the IPL and the EIR.Aerosols of FF with mass median aerodynamic diameters ranging from 2.2 to 3.2 μm were generated with the DustGun aerosol generator. The IPL, perfused in the single-pass mode, was exposed via inhalation to 5.6 and 46 μg of FF. Following inhalation, the perfusate was repeatedly sampled for 100 min, after which the lungs were recovered for quantitation of remaining FF. Two groups of EIR were also exposed via inhalation to 7 μg of FF. One group was immediately euthanized for determination of the initial deposition of FF in the lungs. From the second group, four venous blood samples were drawn up to 4 hr after exposure. The animals were then sacrificed for determination of FF remaining in the lungs.Following inhalation, FF was slowly disappearing from both the IPL and the lungs of the EIR, with a half-life of pulmonary retention of 4.3-4.9 hr for all three exposure series. For the low exposure levels, the concentration curve of FF in the IPL perfusate was similar in shape to that in venous blood of the EIR, with a Cmax of 1.0 and 0.8 nM for the IPL and the EIR, respectively.The results indicate that the IPL and the EIR, when used jointly in PK studies, can provide a detailed characterization of inhaled drugs or toxicants. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|