Effects of St. John's wort extract on indinavir pharmacokinetics in rats: Differentiation of intestinal and hepatic impacts
Journal
Life Sciences
Journal Volume
85
Journal Issue
7-8
Pages
296-302
Date Issued
2009
Author(s)
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. ? 2009 Elsevier Inc. All rights reserved.
Subjects
Bioavailability; Cytochrome P450; Drug-herb interaction; Mechanism
SDGs
Other Subjects
cytochrome P450; Hypericum perforatum extract; indinavir; animal experiment; animal model; animal tissue; article; controlled study; drug bioavailability; drug blood level; drug metabolism; enzyme activity; first pass effect; flow rate; herb drug interaction; high performance liquid chromatography; in vivo study; intestine perfusion; liver; male; nonhuman; rat; small intestine; spectrophotometry; treatment duration; Wistar rat; Animals; Area Under Curve; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Herb-Drug Interactions; HIV Protease Inhibitors; Hypericum; Indinavir; Male; Microsomes, Liver; Plant Extracts; Rats; Rats, Wistar; Time Factors; Animalia; Rattus; Rattus norvegicus
Type
journal article