Model Calculations of Regional Deposition and Disposition for Single Doses of Inhaled Liposomal and Dry Powder Ciprofloxacin
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Model predictions of regional deposition in the respiratory tract are useful in assessing factors that influence the effectiveness of aerosol delivery. Regional deposition models have previously been coupled with models of mucous production and clearance to estimate initial concentrations of drug deposited in the airway surface liquid (ASL) lining tracheobronchial airways. METHODS: Established models of regional deposition and ASL volumes were used to provide input to a new model evaluating the disposition of drug resulting from dissolution or release, absorption, and mucociliary clearance. Additional modeling of oral absorption, distribution, and elimination allowed prediction of systemic exposure. Herein, predicted ASL and plasma concentrations of free (dissolved or unencapsulated) ciprofloxacin over time are reported for a healthy, adult lung model following inhalation of single doses of nebulized liposomal (6 mL of liposomal ciprofloxacin for inhalation, 50 mg/mL, or 6 mL of Pulmaquin, 210 mg; Aradigm) and dry powder (32.5 and 65 mg doses; Bayer) formulations. RESULTS: Over a range of mucous production rates and tracheal clearance velocities, peak ASL concentrations of free ciprofloxacin were consistently greater for Pulmaquin than for other formulations investigated, owing to the presence of free drug in the nebulized Pulmaquin formulation. The time that ASL concentrations of free drug remained above the minimum inhibitory concentration for Pseudomonas aeruginosa was similar for all four formulations. Predicted plasma ciprofloxacin concentration profiles were in good agreement with available data from Phase I trials in healthy volunteers. CONCLUSIONS: Predictions of ASL drug concentrations over time are valuable in elucidating the roles of deposition, drug release or dissolution, and disposition on the effectiveness of inhaled aerosol therapies. For inhaled ciprofloxacin, the present results predict similar ASL concentrations of free drug over time following single doses of inhaled liposomal and dry powder formulations. The impact of multiple doses and airway disease warrants further consideration.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it