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. Author manuscript; available in PMC: 2022 Apr 1.
Published in final edited form as: Expert Opin Drug Metab Toxicol. 2021 Jan 20;17(4):397–412. doi: 10.1080/17425255.2021.1867105

Figure 2.

Figure 2.

Functionally redundant and sequential PK processes are characterized by more than one PK mediator determining drug absorption, distribution, metabolism, and excretion. A drug substrate (SA) may enter a cell via a single uptake transporter (Uptake 1), then leave via a single efflux transporter (Efflux 1) without undergoing any metabolism. Another drug substrate (SB) may enter the cell via a single uptake transporter (Uptake 2), then undergo metabolism by a single metabolizing enzyme (ME 1) before export via a single efflux transporter (Efflux 2). A third drug substrate (SC) may enter the cell via functionally redundant uptake transporters (Uptake 3, Uptake 4, or Uptake 5), then undergo sequential metabolism (ME2 then ME3) before being exported from the cell via functionally redundant efflux transporters (Efflux 3 or Efflux 4). Only three scenarios are depicted, but any combination of redundant and/or sequential transport and/or metabolism is possible, and may include passive diffusion across the membrane.