Identification of drugs that interact with herbs in drug development.

To date, several clinically important drugs have been identified that interact with commonly used herbs. These drugs include (among others) warfarin, midazolam, digoxin, amitriptyline, indinavir, cyclosporine, tacrolimus and irinotecan. Importantly, many of these drugs have very narrow therapeutic indices. Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). Because drug-herb interactions can significantly affect circulating levels of drug and, hence, alter the clinical outcome, the identification of drugs that interact with commonly used herbal medicines has important implications in drug development. In silico, in vitro, animal and human studies are often used to identify drug interactions with herbs. We propose that drug-herb and herb-CYP interaction studies should be incorporated into drug development.