Effects of St. John's Wort Supplementation on Ibuprofen Pharmacokinetics
Bibliographic record
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 (C(max)) values were 131.6 +/- 26.8 microg x h/mL and 31.8 +/- 7.33 microg/mL, respectively, for control samples and 122.4 +/- 32.9 microg x h/mL and 33.6 +/- 7.83 microg/mL, respectively, after St. John's wort treatment. R(-)-ibuprofen mean AUC and C(max) values were 85.1 +/- 26.6 microg x h/mL and 28.4 +/- 8.72 microg/mL, respectively, for control samples and 87.7 +/- 30.1 microg x h/mL and 30.0 +/- 8.97 microg/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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".