TABLE 4.

“Center-of-the-box” parameter values for all simulations

Drug	Active P-gp density T(0) (μM)*	Association to P-gp k11 (M−1s−1)†	Binding constant KB (M−1)‡	Efflux to apical chamber k21(s−1)§	Dissociation to bilayer kr1 (s−1)¶
AMP	50	3 × 109	1300	180	2 × 106
QND	50	3 × 109	6000	16	5 × 105
LPM	50	3 × 109	150	4	2 × 107

^*Simple center-of-the-box value from the consensus range for the three drugs for the concentration of efflux active P-gp in the apical membrane inner monolayer was about T(0) = 5 × 10⁻⁵ M, which will be used for all three drugs.

^†Simple center-of-the-box value from the consensus range for the three drugs was k₁₁ = 3 × 10⁹ M⁻¹s⁻¹, which will be used for all three drugs.

^‡Binding constants were taken as the average value from Table 3, using the high concentration values for loperamide, since that should be due to P-gp.

^§Efflux rate constant k₂₁, from P-gp into the apical chamber, was calculated by the ratio of the fitted k₂₁T(0) for each drug and the center-of-the-box value of T(0) = 5 × 10⁻⁵ M.

^¶Dissociation rate constant k_r1 was calculated by the ratio of the fitted K_B = k₁₁/k_r1 for each drug and the center-of-the-box value of k₁₁ = 3 × 10⁹ M⁻¹s⁻¹.