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首页> 外文期刊>Life sciences >Effects of St. John's wort extract on indinavir pharmacokinetics in rats: differentiation of intestinal and hepatic impacts.
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Effects of St. John's wort extract on indinavir pharmacokinetics in rats: differentiation of intestinal and hepatic impacts.

机译：圣约翰草提取物对茚地那韦药代动力学的影响：肠道和肝脏影响的区分。

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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.
机译：目的：评估圣约翰草（SJW）提取物与茚地那韦在大鼠中可能的草药-药物相互作用，并建立模型来表征口服给药的草药与药物之间相互作用的系统前部位。主要方法：采用体内药代动力学研究和原位单次肠道灌注模型。分别通过高压液相色谱和分光光度法测量血浆茚地那韦浓度和细胞色素P450 3A活性。主要发现：口服150或300毫克/天SJW连续15天可显着降低茚地那韦血浆水平，并具有某些药代动力学参数变化。细胞色素P450 3A分析表明，这种相互作用可归因于茚地那韦代谢的诱导。进一步的灌注研究表明，小肠和肝脏均显着降低了茚地那韦的生物利用度，并且与流速有关。此外，无论是否进行SJW预处理，小肠都是茚地那韦全身前代谢的主要部位。意义：在Wistar大鼠模型中可以清楚地观察到SJW和茚地那韦之间的草药药代动力学相互作用。特别地，可以区分和量化由小肠和肝脏贡献的各自的首过效应。可以设想将动物模型用于研究药草相互作用或其他相关研究目的。

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