Benzalkonium chloride (BAK) is a cationic surfactant preservative used in many multi-dose glaucoma formulations. Clinical observations link preserved therapy to ocular surface disease (OSD), but the quantitative bridge between minute-scale tear exposure and month-to-year dysfunction remains unclear. We developed a coupled, multi-timescale pharmacokinetic/pharmacodynamic (PK/PD) model integrating (a) capacity-limited drop retention with dynamic tear volume and biphasic clearance (overflow/reflex followed by basal turnover, with optional nocturnal suppression), (b) BAK speciation into free monomer capped by an uncertain critical micelle concentration (CMC) plus micellar excess, (c) rapid-equilibrium partitioning of monomeric BAK into tear proteins, soluble mucins, a slow-clearing surface-adherent glycocalyx reservoir, and epithelial membrane binding sites, and (d) membrane-driven internalization to an intracellular pool with slow clearance. For pharmacodynamics, we introduce fast stress and slow burden ('memory') states driven by monomer-membrane interaction and supra-CMC exposure and opposed by recovery/repair; normalized resistance is mapped from stress using a steep Hill relationship calibrated to ECIS barrier-threshold behavior in human corneal epithelial cells. Representative single-dose simulations (0.02% BAK, 40 μL) predict immediate overflow, rapid membrane-site saturation, and front-loaded cellular delivery (about 90-99% within ~30-60 min), with dry-eye-like physiology producing higher retained dose and greater cumulative delivery. Chronic regimen simulations rank risk directionally as dry-eye and night-including dosing > normal and morning-only dosing, while sensitivity screening identifies nominal BAK concentration, membrane capacity/uptake, and nocturnal tear turnover suppression as dominant drivers. This framework provides a quantitative platform for comparing formulations and dosing schedules under explicit uncertainty and for designing calibration experiments (repeated-pulse ECIS and intracellular burden assays) that constrain key parameters governing long-term tolerability.