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Translational model to predict pulmonary pharmacokinetics and efficacy in man for inhaled bronchodilators.
Hendrickx, Ramon; Lamm Bergström, Eva; Janzén, David L I; Fridén, Markus; Eriksson, Ulf; Grime, Ken; Ferguson, Douglas.
Afiliação
  • Hendrickx R; DMPK, Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Lamm Bergström E; DMPK, Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Janzén DLI; DMPK, Cardiovascular and Metabolic Diseases, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Fridén M; DMPK, Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Eriksson U; Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Grime K; DMPK, Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
  • Ferguson D; DMPK, Oncology, IMED Biotech Unit, AstraZeneca, Boston, Massachusetts, USA.
CPT Pharmacometrics Syst Pharmacol ; 7(3): 147-157, 2018 03.
Article em En | MEDLINE | ID: mdl-29280349
ABSTRACT
Translational pharmacokinetic (PK) models are needed to describe and predict drug concentration-time profiles in lung tissue at the site of action to enable animal-to-man translation and prediction of efficacy in humans for inhaled medicines. Current pulmonary PK models are generally descriptive rather than predictive, drug/compound specific, and fail to show successful cross-species translation. The objective of this work was to develop a robust compartmental modeling approach that captures key features of lung and systemic PK after pulmonary administration of a set of 12 soluble drugs containing single basic, dibasic, or cationic functional groups. The model is shown to allow translation between animal species and predicts drug concentrations in human lungs that correlate with the forced expiratory volume for different classes of bronchodilators. Thus, the pulmonary modeling approach has potential to be a key component in the prediction of human PK, efficacy, and safety for future inhaled medicines.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Broncodilatadores / Pulmão Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Broncodilatadores / Pulmão Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article