Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs

Drug metabolism can be influenced by a drug's physicochemical properties, like molecular size and shape, which dictate the drug's interaction with metabolic enzymes.

The drug's pK_a affects ionization, while lipophilicity influences its enzyme interaction and metabolism.

The drug's steric and electronic attributes can alter its enzyme reactivity, impacting metabolism. The stereochemistry of a drug can influence how metabolic enzymes process it.

The induction of drug-metabolizing enzymes can increase drug metabolism. Enzyme inducers, like phenobarbital, rifampicin, and phenytoin, are lipophilic, have long elimination half-lives, and are substrates for the induced enzymes.

Enzyme induction can decrease the drug's pharmacological activity or enhance metabolite activity.

Conversely, inhibiting these enzymes can reduce drug metabolism, with inhibitors being either direct or indirect. One example is the monoamine oxidase inhibitor phenelzine.

Environmental chemicals, like polycyclic aromatic hydrocarbons, can also induce drug-metabolizing enzymes, affecting drug metabolism.