Orange juice has no effect on CYPM6-dependent drug-metabolism

Citrus juices can interact with a number of medications. As little as 250 ml of grapefruit or orange juice can change the metabolism of drugs. Most drugs affected by citrus juices are known to be metabolized by CYP3A4. Recently, some studies have shown an in vitro inhibition of CYP2D6 metabolism by grapefruit juice. CYP2D6 enzyme is an important factor in the metabolism of 20-25% of clinically important drugs, such as antidepressants, neuroleptics, antiemetics, cardiologic drugs and opioids. The aim of our study was to investigate the effects of orange juice on human cytochrome CYP2D6 enzyme activity. The study involved twenty unrelated healthy volunteers. Ten of them received 250 ml (one glass) of orange juice daily for 5 days. Control group consisted of ten persons who received 250 ml (one glass) of tap water. The CYP2D6 phenotype was analyzed before and after 5 days of juice/water ingestion, using sparteine as a model drug. Sparteine and its metabolites were determined in urine by the method of Eichelbaum. Metabolic ratio (MR) was calculated as the ratio of amount of parent drug to the total amount of metabolites. Mean MR, measured after 5 days of drinking the juice, increased by only 7% in group receiving orange juice, and by 10% in control group receiving tap water. Our results suggest that orange juice has no significant influence on metabolism and excretion of CYP2D6-dependent drugs. So it is not necessary to advise patients against drinking orange juice at the same time when they take those drugs.