Chapter 17 - Herb and Drug Interaction

Abstract

Herbal medicines have been widely used since ancient times for the treatment of various ailments, and are now gaining popularity worldwide as complementary or alternative treatments for a variety of diseases. Since herbal medicines are regarded as safe, they are often coadministered with many prescribed drugs, and thereby arises the potential of herb–drug interactions (HDIs). Herbal drugs contain more than one pharmacologically active ingredient, which also contributes to HDIs. Simultaneous use of herbs may increase or decrease the effect of prescribed drugs, which can have very serious consequences. The possibility of HDIs had been largely ignored, but the finding that grapefruit juice could impair drug metabolism forced the scientific fraternity to look at the problem more closely. These interactions could be ascribed to both pharmacokinetic and/or pharmacodynamic mechanisms. A significant proportion of reported HDIs are of pharmacokinetic origin, arising from the effects of herbal medicines on metabolic enzymes and/or transporters. Pharmacokinetic alterations may result in changes in absorption, distribution, metabolism, and excretion of the concomitantly prescribed drugs. These changes are clinically very significant as pharmacokinetic parameters such as the area under the plasma concentration–time curve, the maximum plasma concentration, or the elimination half-life of the concomitant drug alter. Induction or inhibition of metabolic enzymes such as cytochrome P450 (CYP3A4, CYP2C9, CYP1A2) and modulation of efflux transporters (P-glycoproteins) are usually the common mechanisms involved in pharmacokinetic interactions. St. John's wort (SJW; Hypericum perforatum) was a widely used herbal medicine for the treatment of affective disorders such as depression and anxiety, until its propensity to cause drug interactions was known. Its active constituents such as hyperforin and amentoflavone induced intestinal P-glycoprotein and hepatic CYP3A4 enzyme, which markedly increased the metabolism of their cosubstrates. SJW is a potent uptake inhibitor of neurotransmitters such as serotonin, norepinephrine, and dopamine. In combination with other drugs that may elevate serotonin levels (serotonin reuptake inhibitors), SJW may contribute to serotonin syndrome, a potentially life-threatening adverse drug reaction. Thus to increase the safety of herbal drug usage the potential for HDI should always be assessed in the preclinical safety assessment phase of the drug development process. More clinically relevant research is also necessary in this domain as the present information on HDI is insufficient for clinical applications.