Drug interaction between St. John's wort and cyclosporine.
OBJECTIVE
To report a probable drug interaction between the herbal dietary supplement St. John's wort and cyclosporine.


METHODS
A 29-year-old white woman who received a cadaveric kidney and pancreas transplant, with stable organ function and stable cyclosporine concentrations began self-medicating with St. John's wort. After taking St. John's wort supplements for four to eight weeks, her cyclosporine concentrations became subtherapeutic; this was associated with organ rejection. Four weeks after stopping St. John's wort, her cyclosporine concentrations again became therapeutic. Subsequent to this rejection episode, she has developed chronic rejection and now has returned to dialysis.


CONCLUSIONS
St. John's wort is suspected to be a significant inducer of CYP3A4 isoenzyme activity and of P-glycoprotein (P-gp) expression, both of which are important in the metabolism and absorption of cyclosporine. Cyclosporine exhibits a relatively small therapeutic window and is sensitive to medications that can modulate the CYP3A4 isoenzyme and P-gp in both the liver and small intestines.


CONCLUSIONS
Patients taking St. John's wort concomitant with other prescription medications whose absorption and metabolism are mediated by the CYP3A4 isoenzyme and P-gp require close monitoring. Patient medication histories should include inquiries into the use of herbal dietary supplements.
Barone
G W
GW
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205, USA. baronegary@exchange.uams.edu
Gurley
B J
BJ
Ketel
B L
BL
Lightfoot
M L
ML
Abul-Ezz
S R
SR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D016377:Organ Transplantation; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human