Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 374

P08-116 - Grapefruit juice and intestinal drug metabolism

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Grapefruit juice (GFJ) ingestion improves human health but shall be excluded when on medication with specific drugs. This well-known fact is often difficult to explain to patients or students especially since there is the misconception that drug metabolism would mainly be affected in the hepatocytes. The objective is to interrelate published data and to generate a simplified graph which clarifies how GFJ interferes with drug metabolism in human enterocytes and explains possible toxic effects when the oral drug dosage is not lowered.

Methods:
Clincal studies or experiments using human intestinal cells are included. Different types of GFJ are studied and their purified bioactive compounds: flavonoids and furanocourmarins. Results regarding GFJ and concomitant drug metabolism by cytochromes P450 (CYP) are combined with the data obtained when GFJ interferes with drug transport by apical plasma membrane transporters.

Results:
The CYP profile in human small intestine shows a different profile when compared to the liver and contains mainly CYP 3A. CYP activities related to specific drug degradation are inhibited after ingestion of one glass of GFJ. The time line shows a bioactive effect after 4 hours which lasts up to 24 hrs or more. At the same time GFJ reduces the activity of the enterocyte efflux transporter P glycoprotein which is an ABC-transporter that actively pumps lipophilic molecules back into the intestinal lumen. The inhibition of CYP degradation of specific drugs and the reduction of their release back into the intestinal lumen leads to an increased area under the plasma concentration time curve (AUC) by GFJ. Other intestinal transporters like the organic anion-transportitn polypeptide (OATP) are currently studied regarding interference of drug transport by GFJ and many other fruit juices.

Conclusion:
The inhibited pre-systemic drug metabolism occuring in the enterocytes explains how GFJ leads to increased AUC of specific drugs. It also points out that co-administration of GFJ with certain drugs can be beneficial in two aspects: increased bioavailability at lower oral dosage as well as the many beneficial health effects of GFJ.




Funding Source: There was not funding for this research

CoAuthors: Diana Varela-Margolles – SGU Medical School Grenada; Jane Rugh – Self employed

Margit E. Trotz

Professor of Biochemistry
St. Georges University St. Georges True Blue West Indies
Renfrew, Pennsylvania