Submitted to: Expert Opinion on Drug Metabolism & Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2011
Publication Date: 3/3/2011
Citation: Hanley, M.J., Cancalon, P., Widmer, W.W., Greenblatt, D.J. 2011. The effect of grapefruit juice on drug disposition. Expert Opinion on Drug Metabolism & Toxicology. 7(3):267-286. Interpretive Summary: Since the early 1990's, components in grapefruit juice have been shown to inactivate intestinal CYP3A4 enzyme and increase the bioavailability of orally-administered drugs metabolized by CYP3A4. Grapefruit juice can also decrease the bioavailability of a few drugs that rely on organic anion-transporting (OAT) polypeptides in the gastrointestinal tract for their uptake.However, the number of drugs that have been found to interact with grapefruit juice in vitro is far greater than the number of grapefruit juice-drug in-vivo interactions that are clinically relevant. For the majority of patients, complete avoidance of grapefruit juice is unwarranted.
Technical Abstract: Since their initial discovery in 1989, grapefruit juice-drug interactions have received extensive interest from the scientific, medical, regulatory, and lay communities. Although knowledge regarding the effects of grapefruit juice on drug disposition continues to expand, the list of drugs studied in the clinical setting remains relatively limited. This article reviews the in vitro effects of grapefruit juice and its constituents on the activity of cytochrome P450 enzymes, organic anion-transporting polypeptides, P-glycoprotein, esterases and sulfotransferases. The translational applicability of the in vitro findings to the clinical setting is discussed for each drug metabolizing enzyme and transporter. Reported area under the plasma concentration-time curve ratios for available grapefruit juice-drug interaction studies are also provided. Relevant investigations were identified by searching the Pubmed electronic database from 1989 to 2010. Grapefruit juice increases the bioavailability of some orally-administered drugs that are metabolized by CYP3A and normally undergo extensive presystemic extraction. In addition, grapefruit juice can decrease the oral absorption of a few drugs that rely on organic anion-transporting polypeptides in the gastrointestinal tract for their uptake. The number of drugs shown to interact with grapefruit juice in vitro is far greater than the number of clinically relevant grapefruit juice-drug interactions. For the majority of patients, complete avoidance of grapefruit juice is unwarranted.