Review article: cytochrome P450 enzyme, and transport protein mediated herb-drug interactions in renal transplant patients: grapefruit juice, St John's Wort - and beyond!
OBJECTIVE
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.


CONCLUSIONS
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.
Nowack
Rainer
R
Center for Nephrology and Dialysis, Lindau/Bodensee, Germany. nowack@dialyse-lindau.de
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001628:Beverages / Q000009:adverse effects; D032083:Citrus paradisi; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis; D065692:Cytochrome P-450 CYP3A Inhibitors; D004790:Enzyme Induction; D019317:Evidence-Based Medicine; D018565:Food-Drug Interactions; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D028321:Plant Preparations / Q000009:adverse effects; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D015854:Up-Regulation
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065692:Cytochrome P-450 CYP3A Inhibitors; D007166:Immunosuppressive Agents; D028321:Plant Preparations; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human