Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly -: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba
Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly -: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba
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DOI：
10.2165/00002512-200522060-00006
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发表时间：
2005-01-01
期刊：
影响因子：
2.8
通讯作者：
Ang, CYW
中科院分区：
文献类型：
--
作者：
Gurley, BJ;Gardner, SF;Ang, CYW
目的：老年患者更有可能同时服用处方药和植物补充剂，因此可能容易受到草药相互作用的影响。植物化学介导的细胞色素P450(CYP)活性的调节可能是许多草药相互作用的基础。一些证据表明，老年人的细胞色素P450活性可能会降低。如果是这样的话，草药介导的CYP活性变化在这一人群中可能具有更大的临床相关性。本研究以单时间点、表型代谢率为指标，研究长期补充麦芽汁、大蒜油、人参、银杏叶对老年受试者细胞色素P450酶活性的影响。方法：12名60~76岁(平均67岁)的健康志愿者随机分为两组，每组28天，30天为洗脱期。在补充前和补充结束时分别给予咪达唑仑、咖啡因、氯唑沙宗和地布里异喹的探针剂鸡尾酒。用1-羟基咪唑仑/咪达唑仑血清比值(1h)、对黄嘌呤/咖啡因血清比值(6h)、6-羟基氯唑沙宗/氯唑沙宗血清比值(2h)和去氢异喹尿得率(8h)分别测定补充前和补充后的细胞色素P450 3A4、细胞色素P1A2、细胞色素P2E1和细胞色素P450 2D6的表型比值。结果：比较圣约翰麦汁前后的表型比率发现，显著诱导了细胞色素P3A4(约为140%)和细胞色素P42E1酶活性(约为28%)。大蒜油可抑制约22%的细胞色素P450-2E1酶活性。人参对CYP2D6的抑制有统计学意义，但其影响的程度(约为7%)似乎与临床无关。这项研究中测试的补充剂似乎都不会影响CYP1A2的活性。结论：老年人和他们的年轻人一样，容易受到草药介导的CYP活性的影响，特别是那些涉及圣约翰草的补充剂。由CYP活性变化引起的药代动力学草药相互作用可能会对药物疗效和/或毒性产生不利影响。与早期使用年轻受试者的研究相比，这些数据表明，CYP对植物补充剂的反应性可能存在一些与年龄相关的变化。因此，应强烈建议老年人在服用处方药的同时摄入植物补充剂。
Objectives: Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects.Methods: Twelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported 'active' phytochemicals was determined for each supplement.Results: Comparisons of pre- and post-St John's wort phenotypic ratios revealed significant induction of CYP3A4 (approximate to 140%) and CYP2E1 activity (approximate to 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (approximate to 7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity.Conclusions: Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John's wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.