Many substrates, by virtue of their relatively high lipophilicity, remain nonspecifically bound to the lipid membrane of the endoplasmic reticulum. In this state, they may induce microsomal enzymes and may competitively inhibit metabolism of a simultaneously administered drug. Such drugs include various sedative-hypnotics, tranquilizers, anticonvulsants and insecticides.

For example, patients given routine barbiturate therapy may require considerably higher doses of warfarin when being treated with this oral anticoagulant to maintain a prolonged prothrombin time. On the other hand, discontinuation of the sedative may result in reduced metabolism of the anticoagulant and bleeding (a toxic effect of the enhanced plasma levels of the anticoagulant). Similar interactions have been observed in individuals receiving various combination drug regimens such as tranquilizers or sedatives with contraceptive agents and sedatives with anticonvulsant drugs.

An inducer may also enhance its own metabolism. Thus, continued use of a drug may result in one form of tolerance, a progressively reduced effectiveness due to enhancement of its own metabolism.

Conversely, simultaneous administration of two or more drugs may result in impaired elimination of the more slowly metabolized drug and prolongation or potentiation of its pharmacologic effects. Both competitive substrate inhibition and irreversible substrate-mediated enzyme inactivation may augment plasma drug levels and lead to toxic effects from drugs with narrow therapeutic indices.

Impairment of metabolism may also result if a simultaneously administered drug irreversibly inactivates a common metabolizing enzyme, as in the case with secobarbital or novonal (diethylpentenamide) overdoses. These compounds, in the course of their metabolism by cytochrome P-450, inactivate the enzyme and result in impairment of their own metabolism and that of other cosubstrates.