TABLE 8

Theoretical calculation of Kp,uu,true, Kp,uu,V0, and Kp,uu,ss using the calculated ΔΨ

DrugLotKp,uu,trueaKp,uu,V0aKp,uu,ssaRV0/truebRss/trueb
PitavastatinHu807590.71981062.181.17
TFF8.3518.39.752.181.17
RosuvastatinHu807572.419971.92.740.994
TFF1.263.451.252.740.994
PravastatinHu807517.954.515.23.050.850
TFFNot calculatedc
  • a Theoretical values of Kp,uu,true, Kp,uu,V0, and Kp,uu,ss were calculated by Supplemental Equations 6, 8, and 11, respectively. The fi,ion, fo,ion, fi,uion, fo,uion, λ (Table 1), Vmax/Km (Table 5), and PSdif,inf,uion in each lot of human hepatocytes determined by fo,ion, fo,uion, λ, and PSdif (Table 5), according to eq. 7, were used for the calculation.

  • b RV0/true = Kp,uu,V0/ Kp,uu,true and Rss/true = Kp,uu,ss/ Kp,uu,true were calculated by eqs. 11 and 12.

  • c Not calculated for Lot TFF because kinetic parameters (Km, Vmax, and PSdif) of pravastatin were not determined (Table 5).