Abstract
Objective: To evaluate the utility of nasosorption, a non-invasive airway sampling method to collect nasal mucosal lining fluid (MLF), to assess the partitioning of omalizumab (OMZ) (Xolair®, an anti-IgE IgG1 mAb) in nasal MLF in patients.
Methods: Time-matched serum (n=52) and nasosorption samples were sequentially collected (right nostril 1st, and then left) from 8 patients receiving OMZ. Guided by the population pharmacokinetic (PK)-pharmacodynamic model, the PK sampling scheme was customized for each regimen to capture one entire dosing cycle. Nasal MLF samples were collected using the NasosorptionTM FX-i device and then eluted with optimized elution buffer. OMZ and urea in the serum and nasal MLF samples were analyzed using qualified immunoassay and LC-MS assay developed at Genentech. Individual nasal concentrations of OMZ were normalized by the corresponding urea ratio (serum:nasal) at that time point to adjust for the dilution factor from nasosorption elution.
Results: OMZ was detectable in nasal MLF after treatment and the median nasal MLF:serum partitioning was 0.52%, confirming that the drug was able to reach the nasal MLF. The median nasal PK from the left nostril (collected 2nd) was lower than that from the right nostril (collected 1st) (0.17 vs. 0.25 ug/mL), possibly due to the dilution by tears induced by the 1st sampling.
Conclusion: Nasosorption sampling of the nasal MLF is a useful and non-invasive approach to inform drug partitioning to the upper airway, and could enable more accurate predictions of efficacious doses for drugs targeting airway diseases. The ability of OMZ to reach the nasal MLF at detectable concentrations is encouraging for its potential to treat nasal diseases.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA1657.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019