Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients.
BACKGROUND
This study investigated the effect of St John's wort (SJW) extract on the pharmacokinetics of the immunosuppressants tacrolimus (TAC) and mycophenolic acid (MPA).


METHODS
Ten stable renal transplant patients received 600 mg SJW extract for 14 days in addition to their regular regimen of TAC and mycophenolate mofetil.


RESULTS
Dose-corrected AUC((0-12)) of TAC decreased significantly from 180 ng/ml/h at baseline to 75.9 ng/ml/h after 2 weeks of SJW treatment. To maintain therapeutic TAC concentrations, dose adjustments from a median 4.5 mg/day at baseline to 8.0 mg/day under SJW treatment were required. Two weeks after discontinuation of SJW, TAC doses were reduced to a median of 6.5 mg/day. MPA pharmacokinetics remained unaffected by comedication with hypericum extract.


CONCLUSIONS
Administration of SJW extract to patients receiving TAC treatment can result in a serious drug interaction leading to markedly reduced TAC blood concentrations associated with the risk of organ rejection.
Mai
Ingrid
I
Institute of Clinical Pharmacology, University Medical Center Charité, Humboldt University of Berlin, Berlin, Germany. ingrid.mai@charite.de
Störmer
Elke
E
Bauer
Steffen
S
Krüger
Hagen
H
Budde
Klemens
K
Roots
Ivar
I
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D020902:Hypericum; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008517:Phytotherapy; D011336:Probability; D011446:Prospective Studies; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014181:Transplantation Immunology / Q000187:drug effects*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus