Fig. 2.

The predicted active drug/active metabolites of prodrugs plasma levels and biliary excretion changes with out or with the presence of inducers or GOF variants or both on metabolizing enzymes. The predicted active drug/active metabolites of prodrugs plasma levels and biliary excretion changes without (a-1/a-2) or with the presence of inducers or GOF variants (b-1/b-2) or both (c-1/c-2) on metabolizing enzymes. a-1/a-2 represent the normal scenario with no interacting drug or genetic variant. In b-1/b-2 either an inducer drug or gain-of-function variant (GOF) in the metabolizing enzyme, results in increased metabolism to inactive metabolites, and decreased (b-1)/increased (b-2) active drug in the systemic circulation. In c-1/c-2 the presence of inducer drug and the GOF genetic variant combine to produce greater decrease(c-1)/increase(c-2) in the systemic concentration of active drug