In the current study, an extended 3-pore model (TPM) is presented and applied to the problem of optimizing automated peritoneal dialysis (APD) with regard to osmotic water transport (UF), small/middle-molecule clearance, and glucose absorption. Methods: Simulations were performed for either intermittent APD (IPD) or tidal APD (TPD). IPD was simulated for fill and drain volumes of 2 L, whereas TPD was simulated using a tidal volume of 0.5 L, 1 L, or 1.5 L with full drains and subsequent fills (2 L) occurring after every fifth dwell. A total of 25 cycles for a large number of different dialysate flow rates (DFR) were simulated using 3 different glucose concentrations (1.36%, 2.27%, and 3.86%) and 3 different peritoneal transport types: slow (peritoneal equilibrium test D/Pcrea < 0.6), fast (peritoneal equilibrium test D/Pcrea > 0.8), and average. Solute clearance and UF were simulated to occur during the entire dwell, including both fill and drain periods. Results: It is demonstrated that DFRs exceeding ∼ 3 L/h are of little benefit both for UF and small-solute transport, whereas middle-molecule clearance is enhanced at higher DFRs. The simulations predict that large reductions (> 20%) in glucose absorption are possible by using moderately higher DFRs than a standard 6 × 2 L prescription and by using shorter optimized “bi-modal” APD regimens that alternate between a glucose-free solution and a glucose-containing solution. Discussion: Reductions in glucose absorption appear to be significant with the proposed regimens for APD; however, further research is needed to assess the feasibility and safety of these regimens.