Cochlear PK/PD — validated parameters
Source agent: Domain 1 (Sonnet 4.6), 2026-04-23. Consumer: hydrogel_phase4e_cochlear_pkpd.py + any future delivery model for h03/h04/h06/h09.
Parameter table
| Parameter | Literature value | Source (page/table) | Conditions | Status | Used in |
|---|---|---|---|---|---|
| Human scala tympani volume | 34.2 ± 7 μL (range 23–50, n=30) | 2021-dhanasingh-scala-tympani-volume (Front Surg, μCT cadaveric) | Human | ✅ primary | h09 Phase 4e |
| Total human perilymph (ST + SV) | ~93 μL | 2016-ekdale-human-cochlear-hydrodynamics (μCT FE model) | Human | ✅ primary | h09 Phase 4e |
| Middle ear gentamicin t½ | ~70–75 min (k ≈ 0.55/h) | 2018-salt-plontke-pharmacokinetic-principles-inner-ear Fig 4 | Intratympanic, human data | ✅ primary | h09 Phase 4e |
| Middle ear dex-phosphate t½ | ~40 min (k ≈ 1.0/h) | 2018-salt-plontke-pharmacokinetic-principles-inner-ear Fig 4 | Intratympanic | ✅ primary | h09 Phase 4e |
| RWM permeability (TMPA, low-MW ion) | 1.9 × 10⁻⁸ cm/s | 2001-salt-ma-quantification-rwm-permeability (paywalled abstract + PubMed) | Guinea pig | ⚠ paywall (full text needed) | h09 Phase 4e baseline |
| ST clearance t½ (small molecules, guinea pig) | 60 min (k ≈ 0.69/h) | 2001-salt-ma-quantification-rwm-permeability | Guinea pig | ⚠ species scaling | h09 Phase 4e |
| Cochlear aqueduct CSF entry | ~30 nL/min | 2015-salt-hartsock-perilymph-kinetics-fitc-dextran (J ARO, guinea pig) | Guinea pig | ✅ primary | h09 Phase 4e |
| Large-dextran (70 kDa) perilymph t½ | 230 min (k ≈ 0.18/h) | 2015-salt-hartsock-perilymph-kinetics-fitc-dextran | Guinea pig | ✅ primary | h09 Phase 4e |
| ST→tissue fast exchange t½ | 6 min | 2015-salt-hartsock-perilymph-kinetics-fitc-dextran | Guinea pig | ✅ primary | — |
| Serpin fraction of perilymph protein | 27.8% | 2010-bhatt-proteomics-perilymph-csf | Mouse | ✅ primary | suggests peptide proteolysis is attenuated |
Red flags in current h09 Phase 4e model
| Model constant | Value | Problem |
|---|---|---|
K_RWM = 0.02/h | 2%/h for 14 kDa peptide | Citation phantom. Claims “Salt 2011”; no such paper with MW scaling found. Stokes-Einstein scaling TMPA (200 Da, 1.9e-8 cm/s) → 14 kDa gives 0.002–0.004/h — 5–10× lower than model. |
PERILYMPH_VOL_UL = 70 | 70 μL | Unsourced. Real values: 34 μL (ST only, RWM-accessible) or 93 μL (total ST+SV). |
K_CLEAR_MIDDLE_EAR = 0.35/h | 2h t½ | Too slow vs literature (0.55–1.0/h measured). For a gel depot, mechanism is zero-order release, not first-order clearance — conflated in current model. |
K_PROTEOLYSIS = 1.4/h | 30 min t½ | No perilymph peptide t½ ever measured. Bhatt 2009 shows perilymph is serpin-rich → proteolysis likely slower. See also rada16-geometry — assembled RADA16 gel t½ is days to weeks, not minutes. |
Translation notes
- TMPA (trimethylphenylammonium) permeability is benchmark for ions; peptide scaling requires MW⁻⁰·⁵ assumption (Stokes-Einstein). Proper estimation requires the original Salt 2001 methods paper (paywalled, need institutional access).
- Washington University Cochlear Fluids Simulator (http://oto2.wustl.edu) was offline during retrieval — Wayback Machine may have snapshot with human default params.
Connections
[part-of]_hub (literature-params)[see-also]rada16-geometry (gel proteolysis context)[see-also]STRC Hydrogel Phase 4 Computational Campaign[applies]STRC Synthetic Peptide Hydrogel HTC