Mechanisms and Implication of Drug-Herbal Interactions

It has been well recognized that an increasing percentage of the population is using herbal products for both preventive and therapeutic purposes. Often times the use of herbals is associated with attenuating side-effects produced from therapeutic drugs such as chemotherapeutic regimen. The basis of this usage of herbal products is the concept that being a natural product, the herbal must be safe to use. However, contrary to this perception it has been well documented that significant pharmacokinetic and/or pharmacodynamic effects can occur through herb-drug interaction [1,2] which has led to an increased concern regarding the safety and even toxicity of the coadministration of these products with therapeutic drugs [3-7]. This effect is exacerbated more so for drugs that have a narrow therapeutic index (e.g., warfarin, digoxin, and many chemotherapeutic agents). The mechanisms of herbal-drug interaction are generally pharmacokinetic in nature and result in changes in absorption and metabolism of the therapeutic agent. In addition to the chemical/physical properties of drugs that effect absorption after oral dosing (e.g., lipid/water solubility, molecular size, degree of ionization, etc), the inhibition or induction of drug transporters can have a substantial effect on the amount of drug absorbed. Perhaps the best characterized drug transporter is P-glycoprotein (P-gp) which has been found in the apical membrane of cells in various organs including the gastrointestinal tract, liver, lungs, and kidneys. Active compounds in the herbal product have been shown to function as transporter substrates resulting in either inhibition or induction of P-gp causing either elevated or reduced drug concentrations, respectively [7,8]. These alterations in drug concentration could result in either a sub-therapeutic level of exposure or potentially produce toxic side effects.