| Title | Effects of St. John's wort extract on indinavir pharmacokinetics in rats: differentiation of intestinal and hepatic impacts. | | Author(s) | Ho YF, Huang DK, Hsueh WC, Lai MY, Yu HY, Tsai TH | | Institution | School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan. yfho@ntu.edu.tw | | Source | Life Sci 2009 Aug 12; 85(7-8):296-302. | | MeSH | Animals
Area Under Curve
Cytochrome P-450 CYP3A
Dose-Response Relationship, Drug
HIV Protease Inhibitors
Herb-Drug Interactions
Hypericum
Indinavir
Male
Microsomes, Liver
Plant Extracts
Rats
Rats, Wistar
Time Factors
| | Abstract | AIMS: To evaluate the possible herb-drug interaction of St. John's wort (SJW) extracts with indinavir in rats and to set up a model for characterizing pre-systemic sites for the interactions between orally administered herbs and pharmaceuticals. MAIN
METHODS: The in vivo pharmacokinetic study and in situ single-pass intestinal perfusion model were employed in the research. Plasma indinavir concentration and cytochrome P450 3A activities were measured by high-pressure liquid chromatography and spectrophotometric assays, respectively. KEY
FINDINGS: Oral administration of either 150 or 300 mg/day SJW for 15 days significantly reduced indinavir plasma levels with certain pharmacokinetic parameter changes. The cytochrome P450 3A analysis suggested that this interaction was attributable to the induction of indinavir metabolism. Further perfusion study demonstrated that both small intestine and the liver contributed significantly to the reduction of indinavir bioavailability and was flow rate-dependent. Moreover, the small intestine was the major site for the pre-systemic metabolism of indinavir, whether with or without SJW pretreatment.
SIGNIFICANCE: Herb-drug pharmacokinetic interactions between SJW and indinavir can be clearly observed in the Wistar rat model. Particularly, the respective first-pass effect contributed by the small intestine and the liver could be differentiated and quantified. The application of the animal model to investigating herb-drug interactions or other relevant research purposes is envisioned. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19559714 |
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