Einfluss nichtnutritiver inhaltsstoffe des grapefruitsaftes auf bioverfugbarkeit und wirkung von medikamenten

There is a growing interest in non-nutrient compounds of fruits and vegetables and these compounds are often considered as functional food ingredients. We shall summarize here experimental findings that demonstrate that in particular the flavonoids in grapefruit juice have profound effects on the pharmacokinetics of a variety of drugs. These ingredients can affect drug efficiency but may also induce unwanted side effects. One of the key enzymes in drug metabolism is cytochrome P₄₅₀ (CYP) 3A4 that oxidises a broad spectrum of drugs. Because of this oxidation step the plasma concentration and bioavailability of the active drug is reduced and its elimination is increased. Some components of grapefruit juice - mainly flavonoids - have been shown to be potent inhibitors of CYP 3A4 and reduce its protein levels. As a result of CYP 3A4 inhibition, the bioavailability of most of the drugs studied is enhanced. In addition the p-glycoprotein (p-gp) in intestinal epithelial cells appears to be a target of grapefruit juice ingredients. P-gp is an active efflux pump for a number of drugs that reduces the intestinal absorption rate by secreting the drug back into the gut lumen. Grapefruit juice significantly influences p-gp activity and as a result the bioavailability of drugs can be changed. Grape-fruit juice alters the pharmacokinetics and pharmacodynamics of various classes of orally administered drugs. This may be good in view of the effectiveness of a drug and potential cost saving, but an increased and sustained plasma concentration may also be undesirable within respect of toxicological effects. Although not all active components in grapefruit juice have as yet been identified, the studies summarized here show that there are significant food-drug interactions that must be taken into account when talking about functional food ingredients such as flavonoids.