Isolated Perfused Rabbit Lung as a Model for Intravascular and Intrabronchial Administration of Bronchodilator Drugs II: Isoproterenol Prodrugs

Brazzell, Romulus K.; Kostenbauderx, H.B.

doi:10.1002/jps.2600711122

Cited by 16 publications

(2 citation statements)

References 7 publications

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“…Using the isolated perfused and ventilated rat lung, Ryrfeldt & Nilsson (1976) studied the disposition of terbutaline and its diisobutyric acid ester ibuterol after endotracheal instillation. Similar experiments have been made on the isolated rabbit lung with isoprenaline and two of its ester prodrugs (Brazzell & Kostenbauder 1982). A more extensive investigation on drug absorption from the lung after inhalation in vivo has been made by Schanker and his group (Brown & Schanker 1983;Schanker et al 1986), but their studies did not include bronchodilator drugs.…”

mentioning

confidence: 81%

Pharmacodynamic and Pharmacokinetic Aspects on the Transport of Bronchodilator Drugs Through the Tracheal Epithelium of the Guinea‐Pig

Jeppsson¹,

Roos²,

Waldeck³

et al. 1989

Pharmacology & Toxicology

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An isolated vagus nerve-trachea tube preparation from guinea-pig was used to study the effect kinetics of bronchodilating beta-adrenoceptor agonists. The test compounds were added either into the fluid-filled lumen or into the external medium and they all inhibited, dose-dependently and completely, the vagally induced contractions. The hydrophilic compounds isoprenaline, salbutamol and terbutaline were much less potent when administered intratracheally as compared with extratracheal administration indicating a slow transport through the epithelial layer. For the lipophilic compound, D2489 (the resorcinol derivative of salmeterol), this difference was less pronounced. When terbutaline was administered as its lipophilic diisobutyrate ester prodrug, ibuterol, the difference between the routes of administration was largely eliminated. The inhibitory effect of terbutaline, but not D2489, was readily reversed by washing. Measurements of terbutaline and D2489 in the tracheal tissue and in the external medium after the intratracheal administration of the compounds support the view that a hydrophilic compound slowly passes the epithelium and is not retained in the tissue, whereas a lipophilic compound rapidly passes the epithelium and is retained by the tissue. The isolated vagus nerve-trachea tube preparation of the guinea-pig is well suited for the concommitant study of pharmacodynamic and pharmacokinetic properties of bronchodilator drugs.

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mentioning

confidence: 81%

Pharmacodynamic and Pharmacokinetic Aspects on the Transport of Bronchodilator Drugs Through the Tracheal Epithelium of the Guinea‐Pig

Jeppsson¹,

Roos²,

Waldeck³

et al. 1989

Pharmacology & Toxicology

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“…Rapid absorption and capacity-limited metabolism of isoproterenol and prodrugs thereof were observed following intrabronchial and aerosol administration of drug to the isolated rabbit lung [162,163].…”

Section: Journal Of Nanomaterialsmentioning

confidence: 99%

Evaluating the Controlled Release Properties of Inhaled Nanoparticles Using Isolated, Perfused, and Ventilated Lung Models

Beck-Broichsitter

Schmehl

Seeger

et al. 2011

Journal of Nanomaterials

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Polymeric nanoparticles meet the increasing interest for inhalation therapy and hold great promise to improve controlled drug delivery to the lung. The synthesis of tailored polymeric materials and the improvement of nanoparticle preparation techniques facilitate new perspectives for the treatment of severe pulmonary diseases. The physicochemical properties of such drug delivery systems can be investigated using conventional analytical procedures. However, the assessment of the controlled drug release properties of polymeric nanoparticles in the lung remains a considerable challenge. In this context, the isolated lung technique is a promising tool to evaluate the drug release characteristics of nanoparticles intended for pulmonary application. It allows measurements of lung-specific effects on the drug-release properties of pulmonary delivery systems.Ex vivomodels are thought to overcome the common obstacles ofin vitrotests and offer more reliable drug release and distribution data that are closer to thein vivosituation.

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Metabolism of Isosorbide Dinitrate in the Isolated Perfused Rabbit Lung

Mayer

Lubawy

Kostenbauderx

1983

Journal of Pharmaceutical Sciences

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Isolated Perfused Rabbit Lung as a Model for Intravascular and Intrabronchial Administration of Bronchodilator Drugs II: Isoproterenol Prodrugs

Cited by 16 publications

References 7 publications

Pharmacodynamic and Pharmacokinetic Aspects on the Transport of Bronchodilator Drugs Through the Tracheal Epithelium of the Guinea‐Pig

Pharmacodynamic and Pharmacokinetic Aspects on the Transport of Bronchodilator Drugs Through the Tracheal Epithelium of the Guinea‐Pig

Evaluating the Controlled Release Properties of Inhaled Nanoparticles Using Isolated, Perfused, and Ventilated Lung Models

Metabolism of Isosorbide Dinitrate in the Isolated Perfused Rabbit Lung

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