Gurley Bill J, Gardner Stephanie F, Hubbard Martha A, Williams D Keith, Gentry W Brooks, Carrier Julie, Khan Ikhlas A, Edwards David J, Shah Amit
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy, Little Rock, 72205, USA.
Clin Pharmacol Ther. 2004 Nov;76(5):428-40. doi: 10.1016/j.clpt.2004.07.007.
Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of Citrus aurantium , Echinacea purpurea , milk thistle (Silybum marianum), or saw palmetto (Serenoa repens) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity.
Twelve healthy volunteers (6 women, 6 men) were randomly assigned to receive C aurantium , E purpurea , milk thistle, or saw palmetto for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement.
Comparisons of presupplementation and postsupplementation phenotypic ratios suggested that these particular supplements had no significant effect on CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Phytochemical profiles indicated that C aurantium was devoid of the CYP3A4 inhibitor 6',7'-dihydroxybergamottin. Quantities of fatty acids, flavonolignans, and cichoric acid were consistent with label claims for saw palmetto, milk thistle, and E purpurea , respectively.
Botanical supplements containing C aurantium , milk thistle, or saw palmetto extracts appear to pose a minimal risk for CYP-mediated herb-drug interactions in humans. Although the effects of E purpurea on CYP activity were minor, further study into the interaction potential of this botanical is merited.
植物化学物质介导的细胞色素P450（CYP）活性调节可能是许多草药与药物相互作用的基础。使用单时间点表型代谢率来确定长期补充枳实、紫锥菊、水飞蓟（水飞蓟属）或锯叶棕提取物是否会影响CYP1A2、CYP2D6、CYP2E1或CYP3A4的活性。
12名健康志愿者（6名女性，6名男性）被随机分配接受枳实、紫锥菊、水飞蓟或锯叶棕提取物，为期28天。在每个补充阶段之间设置一个30天的洗脱期。在补充前（基线）和补充结束时，给予咪达唑仑和咖啡因的探针药物鸡尾酒，24小时后再给予氯唑沙宗和异喹胍（国际非专利药品名称，去甲异喹胍）。通过使用1-羟基咪达唑仑/咪达唑仑血清比率（1小时样本）、对黄嘌呤/咖啡因血清比率（6小时样本）、6-羟基氯唑沙宗/氯唑沙宗血清比率（2小时样本）和异喹胍尿回收率（8小时收集），分别测定补充前和补充后CYP3A4、CYP1A2、CYP2E1和CYP2D6的表型特征测量值。测定每种补充剂中所谓“活性”植物化学物质的含量。
补充前和补充后表型比率的比较表明，这些特定的补充剂对CYP1A2、CYP2D6、CYP2E1或CYP3A4的活性没有显著影响。植物化学物质谱表明，枳实不含CYP3A4抑制剂6',7'-二羟基佛手柑内酯。脂肪酸、黄酮木脂素和菊苣酸的含量分别与锯叶棕、水飞蓟和紫锥菊的标签声明一致。
含有枳实、水飞蓟或锯叶棕提取物的植物补充剂在人体内引发CYP介导的草药与药物相互作用的风险似乎最小。虽然紫锥菊对CYP活性的影响较小，但值得对这种植物的相互作用潜力进行进一步研究。
