Part of S: Sensory organs.
Typical structure. For pressure, a physiological baseline built from aqueous humour dynamics, with the drug entering as an effect on those parameters, which is what carries the model from rabbit and dog into patients [1].
Dosing time is design, not noise. Morning and evening instillation of the same fixed combination both lowered 24 hour pressure but differed in fluctuation, so clock time belongs in the model [2].
Vitreous exposure is predicted, not sampled. Faricimab vitreous concentrations were inferred from aqueous humour and plasma samples, with plasma exposure roughly 6000-fold below vitreous [3]. The aflibercept population model was fitted to plasma alone, ocular concentrations being a model output [4].
Plasma reports safety, not effect. Here plasma reports systemic safety, not the driver of effect: ophthalmic timolol is absorbed systemically, and paroxetine raised its plasma exposure 1.6-fold from 0.1% gel and 1.8-fold from 0.5% drops, with standing heart rate significantly lower only after the drops [5]. That makes it a drug interaction question.
References
[1]
Durairaj C, Shen J, Cherukury M. Mechanism-based translational pharmacokinetic-pharmacodynamic model to predict intraocular pressure lowering effect of drugs in patients with glaucoma or ocular hypertension. Pharmaceutical Research 2014;31:2095–106.
https://doi.org/10.1007/s11095-014-1311-9.
[2]
Feng H, Han D, Lu W, Tang G, Zhang H, Fan S, et al. Efficacy of morning versus evening latanoprost/timolol fixed combination for open-angle glaucoma and ocular hypertension: A randomized clinical trial. Translational Vision Science & Technology 2024;13:21.
https://doi.org/10.1167/tvst.13.1.21.
[3]
Diack C, Gibiansky L, Jaminion F, Gibiansky E, Gaudreault J, Bogman K, et al. Ocular pharmacokinetics of faricimab following intravitreal administration in patients with retinal disease. Translational Vision Science & Technology 2024;13:14.
https://doi.org/10.1167/tvst.13.11.14.
[4]
Bihorel S, Chiu J, Chittenden J, Eissing T, Turner KC, Höchel J, et al. Integrated population pharmacokinetic analysis of intravitreal aflibercept drug products. CPT: Pharmacometrics & Systems Pharmacology 2026;15:e70287.
https://doi.org/10.1002/psp4.70287.
[5]
Mäenpää J, Volotinen-Maja M, Kautiainen H, Neuvonen M, Niemi M, Neuvonen PJ, et al. Paroxetine markedly increases plasma concentrations of ophthalmic timolol;
CYP2D6 inhibitors may increase the risk of cardiovascular adverse effects of 0.5% timolol eye drops. Drug Metabolism and Disposition 2014;42:2068–76.
https://doi.org/10.1124/dmd.114.059576.