Inhibitory Effect of Grapefruit Leads to Altered Drug Pharmacokinetics
Grapefruit is known to interact with more than 85 drugs belonging to a diverse range of drug classes. A single glass of grapefruit juice (GFJ) is sufficient to cause a clinically significant drug interaction. Understanding how these interactions occur is vital for predicting and avoiding grapefruit-drug interactions. These interactions result from inhibition of CYP3A4 – a member of the cytochrome P450 enzyme family, P-Glycoprotein (P-gp) – an efflux protein, and Organic Anion-Transporting Polypeptides (OATPs). Therefore, this paper aims to investigate how grapefruit interacts with these pathways to alter drug pharmacokinetics. The results of ten primary papers composed of both clinical and in vitro studies are presented. Repeated consumption of GFJ increases its inhibitory effect on CYP3A4. Additionally, different components of grapefruit (furanocoumarins, naringin/naringenin and bioflavonoids) are responsible for the inhibition of these pathways, causing mechanism-based inhibition of CYP3A4 and competition-based inhibition of P-gp and OATPs. Furthermore, due to their functions, inhibition of CYP3A4 and P-gp increases drug absorption, increasing plasma drug concentrations. Whereas, the reverse results from inhibition of OATPs. The pharmacokinetics of sertraline (anti-depressant), celiprolol (β-inhibitor), atorvastatin (statin), ethinylestradiol (estrogen) and oxycodone (opioid) were found to be altered by grapefruit. These drugs were investigated since they belong to the classes of drugs most commonly prescribed to people over the age 45, the demographic most likely to experience grapefruit-drug interactions. By better understanding grapefruit-sensitive pathways and how they alter drug pharmacokinetics, predictions can be made about other drugs that may interact with grapefruit and whether these pathways are sensitive to other foods.