Figure 1:

(A) Identification and testing of factors in inter-individual PK variability often take a single factor approach (i.e., genes, drugs, natural productNPs, and disease states). (B) A multi-factorial approach to precision drug therapy attempts to account for the sub-populations of patients who experience more complex PK interactions. The overlapping portions of the circles indicate all possible 2-, 3-, and 4-way interactions between factors. The 2-way interactions are shown in white textboxes at the intersection of two circles (except for G-G-DI and D-D-DI, which represent interactions between two polymorphisms in different genes and complex drug interactions, respectively). The relevance of each interaction will depend on the specific metabolizing enzymes or transporters involved and will be determined on a case-by-case basis.