Xu H, Williams K M, Liauw W S, Murray M, Day R O, McLachlan A J
Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
Br J Pharmacol. 2008 Apr;153(7):1579-86. doi: 10.1038/sj.bjp.0707685. Epub 2008 Jan 21.
Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes.
A crossover controlled study was conducted in 21 healthy subjects. Each received gliclazide (80 mg) either alone or during 15 days treatment with St John's wort. The area under the plasma concentration-time curve (AUC(0-infinity)), apparent clearance (CL/F) and elimination half-life (t 1/2) of gliclazide and incremental changes in glucose and insulin AUC(0-4) were compared. CYP2C92 and CYP2C93 alleles were identified using PCR followed by restriction enzyme digestion analysis.
St John's wort significantly altered gliclazide pharmacokinetics in all except for four healthy subjects. The mean ratio and 90% confidence interval (CI) of gliclazide AUC(0-infinity) and CL/F were 0.67 (0.55-0.81) and 1.50 (1.24-1.81), respectively, after St John's wort treatment. St John's wort decreased gliclazide t (1/2), with mean ratio and 90% CI of 0.85 (0.74-0.93). There were no significant changes in glucose or insulin AUC(0-4) after St John's wort treatment and no significant differences according to CYP2C9 genotype.
Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.
患者通常会在服用传统药物的同时服用补充药物，但却没有关于安全性或草药 - 药物相互作用风险的明确证据。本研究的目的是评估在具有不同细胞色素P450 2C9（CYP2C9）基因型的健康受试者中，圣约翰草与格列齐特之间潜在的药代动力学（PK）和药效学（PD）相互作用。
对21名健康受试者进行了一项交叉对照研究。每位受试者单独服用格列齐特（80毫克），或在接受圣约翰草治疗15天期间服用。比较了格列齐特的血浆浓度 - 时间曲线下面积（AUC(0 - ∞)）、表观清除率（CL/F）和消除半衰期（t 1/2），以及葡萄糖和胰岛素AUC(0 - 4)的增量变化。使用聚合酶链反应（PCR）随后进行限制性内切酶消化分析来鉴定CYP2C92和CYP2C93等位基因。
除4名健康受试者外，圣约翰草显著改变了格列齐特的药代动力学。圣约翰草治疗后，格列齐特AUC(0 - ∞)和CL/F的平均比值及90%置信区间（CI）分别为0.67（0.55 - 0.81）和1.50（1.24 - 1.81）。圣约翰草缩短了格列齐特的t(1/2)，平均比值及90%CI为0.85（0.74 - 0.93）。圣约翰草治疗后葡萄糖或胰岛素AUC(0 - 4)无显著变化，且根据CYP2C9基因型无显著差异。
圣约翰草治疗显著增加了格列齐特的表观清除率，这与CYP2C9基因型无关。接受这种联合治疗的糖尿病患者应密切监测，以评估疗效降低的可能迹象。
