Pharmacokinetic simulation of dgRTA-induced permeability. HUV-EC-C monolayer cultures and permeability measurements were performed as in Fig 3. (A) HUV-EC-C monolayers were either left untreated (n = 4; ○) or were treated with 10⁻⁸ mol/L (0.3 μg/mL) dgRTA (n = 2; ▪). (B) HUV-EC-C monolayers were either left untreated (n = 4; ○) or were exposed to varying concentrations of RTA (n = 6; •). The thick-lined curves represent monolayer permeability in terms of the units displayed on the left-hand vertical axis. The actual RTA exposure (broken line) was used to approximate a theoretical exposure (solid, thin line) based on a t_1/2 of 7.8 hours and a peak RTA concentration of 2 μg/mL. Statistically significant differences between the mean responses of treated and time-matched control monolayers are depicted as follows: **P < .01.