| Literature DB >> 30714473 |
Antoine Guillon1,2,3, Jeoffrey Pardessus1,2, Pierre Lhommet4, Christelle Parent1,2, Renaud Respaud1,2,5, Denis Marchand1,2, Jérôme Montharu6, Michèle De Monte6, Philip Janiak7, Christophe Boixel8, Héloïse Audat9, Sylvain Huille9, Etienne Guillot7, Nathalie Heuze-Vourc'h1,2.
Abstract
Therapeutic antibodies (Abs) are emerging as major drugs to treat respiratory diseases, and inhalation may provide substantial benefits for their delivery. Understanding the behavior of Abs after pulmonary deposition is critical for their development. We investigated the pharmacokinetics of a nebulized Ab by continuous sampling in lung parenchyma using microdialysis in non-human primates. We defined the optimal conditions for microdialysis of Ab and demonstrated that lung microdialysis of Ab is feasible over a period of several days. The concentration-profile indicated a two-phase non-linear elimination and/or distribution of inhaled mAbX. Lung exposition was higher than the systemic one over a period of 33 hours and above MabX affinity for its target. The microdialysis results were supported by an excellent relationship with dosages from lung extracts.Entities:
Keywords: Monoclonal antibodies; microdialysis; pharmacokinetics; pulmonary delivery
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Year: 2019 PMID： 30714473 PMCID： PMC6380415 DOI： 10.1080/19420862.2018.1556081
Source DB: PubMed Journal: MAbs ISSN： 1942-0862 Impact factor: 5.857