Review Article: Cytochrome P450 enzyme, and transport protein mediated herb–drug interactions in renal transplant patients: Grapefruit juice, St John's Wort – and beyond! (Review Article)

Abstract

SUMMARY:Aim: To survey the evidence for plant-products to modify cytochrome P450 enzyme, and transport protein mediated drug metabolism in renal transplant patients. Methods: A literature search was performed to identify "in vitro" and "in vivo" research on plant-products that might cause overdosage or loss of efficacy of immunosuppressive drugs in transplant patients by the interaction mechanisms already characterized for grapefruit juice and St. John's Wort. Results: The interaction mechanisms of St. John's Wort by pregnane X-receptor mediated upregulation of cytochrome-P450 enzyme 3A4 and p-glycoprotein expression and of grapefruit juice by mechanism-based inhibition of intestinal CYP3A4 suggest that many other plant products will likewise cause interactions with drugs because they occupy the same metabolic pathways. The respective research on foods, spices and medicinal herbs is listed in a comprehensive table and weighted according to its strength of evidence to cause clinically relevant interactions. Conclusion: Physicians supervising drug-regimes in renal transplant patients should be aware of plant products beyond SJW and GFJ to possibly cause overdosage or failure of drug-treatments by herb-drug interactions.

Are medicinal herbs safe? The opinion of plant vendors from Diadema (São Paulo, southeastern Brazil)

“…Cytochrome P450 (CYP) monooxygenases are probably the most important classes of enzymes in hepatic drug metabolism (Liu et al, 2006) and the list of herbal medicines with a potential for modifying drug bioavailability by inhibition or stimulation of CYP450 enzymes seems endless. For example, St John's wort increases the activity of the CYP3A4 and may lead to a reduction in plasma concentration of a number of medicines, including cyclosporin, statins and hormonal contraceptives (Novack, 2008).…”

Fruit/Vegetable–drug Interactions: Pharmacokinetic Assay With a Cyp3a4 Substrate

“…[18] In the present study, felodipine AUC and K a values were reduced, while clearance was increased for the groups co-administered with paw paw and pumpkin (ugu) vegetable extract. Studies by [19,20] revealed that tangeretin, a flavonoid found in high levels in tangerine juice, stimulates CYP3A4 activity. It was shown to be a potent region-selective stimulator of midazolam 1 ′ -hydroxylation by human liver microsomes CYP3A4.…”

Interactions of Theophylline with Drug, Diet, Some Xenobiotics, and Habits and Their Toxicological Outcomes

“…Bir Sit P450 3A4 inhibitörü olup, diğer Sit P450 izozimleri üzerine etkisiz olduğu bildirilmiştir [35].…”