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. 2020 Sep 25;9(10):571–583. doi: 10.1002/psp4.12553

Figure 6.

Figure 6

Sensitivity analyses of simulated renal clearance (CLr in mL/min) at multiple stages of chronic kidney disease (CKD) reflected by varying glomerular filtration rates (GFR in mL/min) using adaptive model (shown in yellow‐red). (a) The sensitivity analyses of adaptive model‐simulated CLr of neutral unbound permeable drugs (f u,p = 1, P app = 30 × 10‐6 cm/s) with a constant unbound intrinsic apical efflux transport clearance (CLefflux = 150 mL/min) and different unbound intrinsic basolateral uptake transport clearances (CLuptake = 10–3,000 mL/min) across a range of GFRs (5–120 mL/min). (b) The sensitivity analyses of adaptive model‐simulated CLr of neutral unbound permeable drugs (f u,p = 1, P app = 30 × 10‐6 cm/s) with a constant unbound intrinsic basolateral uptake transport clearance (CLuptake = 150 mL/min) and different unbound intrinsic apical efflux transport clearances (CLefflux = 10–3,000 mL/min) across a range of GFRs (5–120 mL/min). The sensitivity analyses using proportional model and the comparison between the two models are shown in the Figure S2 . (c, d) The simulations of CLr of para‐amino‐hippuric (PAH) and memantine in red curves, respectively, using adaptive model, at multiple stages of CKD, and comparison to the observed data (Table S2 ) shown in black open circles with calculated absolute folderror (AFE)A shown in the insets. The simulation results for PAH and memantine using proportional model are shown in Figure S3 .