Mechanisms and Clinical Relevance of Herb–Drug Interactions from the Perspectives of Pharmacokinetics

Type A therapeutic and adverse effects (ADRs) of a drug are related to its concentration at the sites of action, and this is related to the dose, the administration route, and drug’s absorption, distribution, metabolism, and/or excretion. Preclinical and clinical studies that lead to the approval of a new drug provide the information about the right dose(s) and administration route(s) required to obtain the desirable effects without adverse effects. Furthermore, along with the assessment of the pharmacokinetics and long-term safety and efcacy of the drug (benet-risk ratio), these studies identify factors, including age, disease states, genetic polymorphisms, and concomitantly administered drugs, that may alter its pharmacokinetics and thus affect the drug responses. However, unexpected unwanted side effects or, alternatively, lack of

14.1 Introduction .................................................................................................. 243 14.2 Pharmacokinetic Herb-Drug Interactions: Possible Sites of

Interactions and Predicted Outcomes ...........................................................244 14.2.1 Herb-Drug Interactions Involving Membrane Transporters ............245 14.2.2 Herb-Drug Interactions Involving Drug-Metabolizing Enzymes ...... 248

14.3 Evidence for Herb-Drug Interactions Involving Induction of Drug-Metabolizing Enzymes and/or Transporters .......................................249