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COMPLEMENTARY AND ALTERNATIVE MEDICINE

Effects of St. John's Wort Supplementation on Ibuprofen Pharmacokinetics

Assistant Professor, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX

William R Ravis, PhD FCP

Professor/Head, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL

Kimberly Braxton Lloyd, PharmD

Director, Auburn University Pharmaceutical Care Center; Associate Professor, Department of Pharmacy Practice, Auburn University, Auburn, AL

Thomas J Stokes, MD

Internal Medicine and Nephrology, Opelika Nephrology Referral Center, Opelika, AL

Reprints: Dr. Bell, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St., Houston, TX 77004, fax 713/313-1901, bellec{at}tsu.edu

BACKGROUND: St. John's wort is a popular herbal supplement that has been involved in various herb-drug interactions. Experimental findings suggest that the supplement may impact CYP2C9 metabolism. CYP2C9 is responsible for the irreversible metabolism of ibuprofen.

OBJECTIVE: To examine the effect of 3 weeks of St. John's wort administration on the stereoselective pharmacokinetics of ibuprofen.

METHODS: Eight male subjects participated in this study. The single-dose pharmacokinetics of ibuprofen were evaluated before and after 21 days of St. John's wort administration. Plasma ibuprofen concentrations were determined, using a stereoselective, reversed-phase HPLC assay. Model independent methods were used to evaluate the pharmacokinetics of each ibuprofen enantiomer. Data were analyzed by 2 way ANOVA testing and confidence interval testing.

RESULTS: S(+)-ibuprofen mean ± SD AUC and maximum concentration (C_max) values were 131.6 ± 26.8 µg^·h/mL and 31.8 ± 7.33 µg/mL, respectively, for control samples and 122.4 ± 32.9 µg^·h/mL and 33.6 ± 7.83 µg/mL, respectively, after St. John's wort treatment. R(-)-ibuprofen mean AUC and C_max values were 85.1 ± 26.6 µg^·h/mL and 28.4 ± 8.72 µg/mL, respectively, for control samples and 87.7 ± 30.1 µg^·h/mL and 30.0 ± 8.97 µg/mL, respectively, for St. John's wort treatment samples. St. John's wort administration resulted in no significant effects on the C_max and AUC of either stereoisomer. A 31% decrease in S(+)-ibuprofen mean residence time (p = 0.02) was observed.

CONCLUSIONS: St. John's wort administration for 21 days had no apparent clinically important impact on the single-dose pharmacokinetic parameters of S(+)- and R(-)-ibuprofen. Although St. John's wort treatment appears to significantly reduce the mean residence time of S-ibuprofen, no ibuprofen dose adjustments appear warranted when the drug is administered orally with St. John's wort, due to the lack of significant change observed in ibuprofen AUC and C_max for either enantiomer.

Key Words: cytochrome P450 isoenzymes, ibuprofen, St. John's wort, stereoselective

Published Online, February 6, 2007. www.theannals.com, DOI 10.1345/aph.1H602

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