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

Abstract

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 (Cmax) 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 Cmax 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 Cmax 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 Cmax for either enantiomer.