S: Sensory organs
Drugs applied to the eye and the ear. The notes below come from S01, ophthalmologicals, where the difficulty is an organ of limited accessibility, for administering drug and for sampling tissue [1].
In 1977 Thom Zimmerman and Herbert Kaufman studied single-dose timolol at four strengths in twenty patients with chronic open-angle glaucoma. Every strength, down to 0.1%, lowered pressure for at least 24 hours, which led them to propose a once a day topical agent [2].
| Level 2 code | Description | In plain terms | Example drug |
|---|---|---|---|
| S01 | Ophthalmologicals | medicines applied to the eye | Latanoprost (S01EE01) / aflibercept (S01LA05) |
| S02 | Otologicals | ear medicines, mostly drops | Ciprofloxacin ear drops (S02AA15) / dexamethasone with antiinfectives (S02CA06) |
| S03 | Ophthalmological and otological preparations | drops licensed for both eye and ear | Residual group for drops licensed for both eye and ear; no separate standard of care. Closest is dexamethasone with antiinfectives (S03CA01); single-agent example ciprofloxacin (S03AA07). Eye and ear disease is treated from S01 and S02 instead. |
Modeling notes
Endpoint. In S01E the endpoint is intraocular pressure, read as a 24 hour series rather than one clinic value, because the baseline itself carries a circadian rhythm [3]. Posterior segment endpoints vary: the pegcetacoplan analysis used geographic atrophy lesion area [4], the faricimab analysis best corrected visual acuity [5].
Easy to overlook. For faricimab, vitreous elimination is the slowest step, so vitreous, aqueous and plasma concentrations decline in parallel and the plasma curve reports ocular release rather than systemic clearance [5].
Mechanistic extrapolation. Ocular PBPK is used for tissue too invasive to access in humans: atropine, predicted to penetrate the posterior segment after topical dosing [6], and an ofloxacin ointment, extrapolated from rabbit aqueous humour to human ocular exposure [7]. Ocular QSP exists but is still assembling its data and cellular systems [1].