Fig 2. The influence of the EPR effect on the rate of tumor uptake of Doxil for an administered dose of 100 mg (50 mg m^-2).

(A) Pharmacokinetics for Doxil. Symbols are data from a clinical trial reported by Gabizon et al. [12]. The solid red line is obtained from our model using values for k_p, k_d, and k_el derived from median values of A, B, α, and β reported by Gabizon et al. (Table 1) [12], where k_el ~ k₁₀ when k_el >> k_epr. The dotted lines represent the pharmacokinetics for the minimum and maximum values of A, B, α, and β. (B) Simulations of the pharmacokinetics for Doxil with k_epr/k_el = 0, 10^–1, 10^–2, and 10^–3, and k_b = 0. (C) Amount of Doxil in tumor for k_epr/k_el = 10^–1, 10^–2, 10^–3, and 10^–4, and k_b = 0. (D) Amount of Doxil in tumor for k_epr/k_el = 10^–3 and k_b/k_epr = 0, 10, 100, 1000. The amount of Doxil in tumor represents the total amount of doxorubicin.