English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A population PK model was developed to characterize the time-course of ASN-1 and ASN-2 in ELF following intravenous administration of ASN100 in healthy subjects. Methods A total of 42 healthy subjects received a single dose of ASN-1 or ASN-2 alone (200–4,000 mg) or ASN100 (3,600 or 8,000 mg; 1:1 ratio of ASN-1:ASN-2). All subjects contributed 13–17 serum samples for ASN-1/ASN-2 assay. Twelve subjects contributed 2 bronchoalveolar lavage (BALF) samples each for ELF concentration assay (Day 1 or 2 and Day 8 or 30 after dosing). A previously reported, linear, two-compartment population PK model for serum [ID Week 2017, Poster #1849] was expanded and fit to the ELF concentration–time data. Sequential analysis was used to fix serum PK as the driver for ELF PK; only those parameters controlling transfer into and out of the ELF were fit. Results An effect-site model adequately described the time-course of ELF concentrations. To allow for estimation of interindividual variability in the elimination from ELF, residual variability in ELF was fixed to that previously estimated for the serum PK data. Separate rate constants for transfer from serum to ELF were estimated for the 3,600 and 8,000 mg ASN100 dose groups to reflect the less than dose-proportional increase in ELF concentrations for both ASN-1 and ASN-2. Goodness-of-fit plots did not reveal any appreciable biases. A visual predictive check indicated that the model could adequately capture the observed data (Figure 1). Predicted ELF penetration using the ratio of ELF:serum AUC0–∞ was 33.0% for ASN-1 and 20.3% for ASN-2 following the selected clinical dose of 3,600 mg. Conclusion A population PK model adequately described the time-course of ASN-1 and ASN-2 in ELF. ELF penetration was 20–33% following administration of the ASN100 clinical dose. These results should be interpreted with caution given the limited sample size (six subjects per dose group) and limitations of urea-based normalization of BALF to ELF volume. Disclosures S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. C. Stevens, Arsanis, Inc.: Employee and Shareholder, Salary and stock options. Z. Magyarics, Arsanis Biosciences GmbH: Employee and Shareholder, Salary and stock options. S. A. Luperchio, Arsanis, Inc.: Employee and Shareholder, Salary and stock options. C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support.

open forum infectious diseases

1408. Population Pharmacokinetic (PK) Model to Describe Epithelial Lining Fluid (ELF) Penetration of ASN-1 and ASN-2 after ASN100 Administration to Healthy Subjects