Influence of St. John's Wort on Intravenous Fentanyl Pharmacokinetics, Pharmacodynamics, and Clinical Effects: A Randomized Clinical Trial.
Journal Article (Journal Article)
BACKGROUND: Patients often use complementary and alternative herbal medicines, hence, potential exists for adverse herb-drug interactions. Fentanyl is metabolized by hepatic CYP3A4 and considered transported by blood-brain barrier P-glycoprotein. Both disposition processes could be upregulated by the herbal St. John's wort. This investigation evaluated effects of St. John's wort on fixed-dose and apparent steady-state IV fentanyl pharmacokinetics, pharmacodynamics, and clinical effects. METHODS: Healthy volunteers received a fentanyl fixed-dose infusion and an individually tailored target controlled infusion on separate days, before and after 30-day St. John's wort (300 mg thrice daily; n = 8) or placebo control (n = 8) in a randomized parallel-group design. Fentanyl plasma concentrations, pupil diameter, analgesic response to experimental pain (cold pressor), subjective side effects, and cognitive effects were measured. Plasma fentanyl concentrations and changes in pupil diameter were subjected to pharmacokinetic-pharmacodynamic modeling. RESULTS: St. John's wort did not alter fentanyl pharmacokinetics. Clearance (l/min) before and after St. John's wort (1.13 ± 0.29 and 1.24 ± 0.26, respectively) or placebo (0.96 ± 0.28 and 1.12 ± 0.27, respectively) were not different. St. John's wort also did not affect fentanyl pharmacodynamics as measured by pupil constriction after fixed-dose and tailored fentanyl infusions. EC50 (ng/ml) was 1.1 ± 0.7 and 1.4 ± 0.9 before and after St. John's wort versus 1.2 ± 0.8 and 1.4 ± 1.7 before and after placebo. Effect site equilibration time, T½,ke0 (min), was 12.8 ± 5.3 and 11.3 ± 6.4 before and after St. John's wort versus 11.4 ± 6.4 and 11.1 ± 5.6 before and after placebo. St. John's wort had no influence on analgesia, cognitive performance, or somatic cognitive-affective effects of fentanyl. CONCLUSIONS: St. John's wort did not alter fentanyl pharmacokinetics, pharmacodynamics or clinical effects, suggesting no effect on hepatic clearance or blood-brain barrier efflux. Patients taking St. John's wort will likely not respond differently to IV fentanyl for anesthesia or analgesia.
Full Text
Duke Authors
Cited Authors
- Loughren, MJ; Kharasch, ED; Kelton-Rehkopf, MC; Syrjala, KL; Shen, DD
Published Date
- March 2020
Published In
Volume / Issue
- 132 / 3
Start / End Page
- 491 - 503
PubMed ID
- 31794512
Pubmed Central ID
- PMC7029805
Electronic International Standard Serial Number (EISSN)
- 1528-1175
Digital Object Identifier (DOI)
- 10.1097/ALN.0000000000003065
Language
- eng
Conference Location
- United States