Guiotto P, Woelkart K, Grabnar I, Voinovich D, Perissutti B, Invernizzi S, Granzotto M, Bauer R
Department of Pharmaceutical Sciences, University of Trieste, P.le Europa 1, I-34127 Trieste, Italy.
Phytomedicine. 2008 Aug;15(8):547-54. doi: 10.1016/j.phymed.2008.05.003. Epub 2008 Jun 25.
The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.9 mg) was evaluated in a pharmacokinetic study in humans and the possible effects on the immunological system were measured. Alkamides were found to be rapidly absorbed and measurable in plasma 10 min after administration of 0.21 and 0.9 mg lozenges and remained detectable for 3h for the 0.21 mg lozenges and for more then 3h for the 0.9 mg lozenges; 0.07 mg lozenges were measurable 20 min after administration and remained detectable for only 2h after the administration. A significant dose-independent down-regulation of the pro-inflammatory cytokines IL-12p70, IL-8, IL-6, IL-10 and TNF was observed 24h after oral administration. The results of non-compartmental pharmacokinetic analysis revealed that a C(max) of (0.65+/-0.41 ng/ml) was reached at 32 min with the 0.07 mg lozenges, (1.00+/-0.21ng/ml) at 25 min with the 0.21 mg lozenges and (8.88+/-5.89 ng/ml) at 19 with the 0.9mg lozenges. As evidenced by the dose-exposure relationship, no significant departure from dose proportionality was observed, indicating linearity in pharmacokinetics. To get a further insight in pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides a compartmental population pharmacokinetic model was developed applying mixed effect modelling procedure. The results demonstrate that within the dose range studied pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides are linear and that absorption is very rapid (t(1/2)=6 min) with apparently no lag time, thus indicating the possibility that a fraction of the drug is absorbed through the oral mucosa.
在一项人体药代动力学研究中，评估了紫锥菊植物疗法含片在三种不同剂量水平（0.07、0.21和0.9毫克）下主要烷酰胺类化合物十二碳-2E,4E,8Z,10E/Z-四烯酸异丁酰胺的相对生物利用度，并测量了其对免疫系统的可能影响。发现服用0.21毫克和0.9毫克含片后10分钟，烷酰胺类化合物在血浆中迅速吸收且可检测到，0.21毫克含片在3小时内仍可检测到，0.9毫克含片在3小时以上仍可检测到；服用0.07毫克含片后20分钟可检测到，服用后仅2小时仍可检测到。口服24小时后，观察到促炎细胞因子IL-12p70、IL-8、IL-6、IL-10和TNF有显著的剂量非依赖性下调。非房室药代动力学分析结果显示，服用0.07毫克含片后32分钟达到的C(max)为(0.65±0.41纳克/毫升)，服用0.21毫克含片后25分钟为(1.00±0.21纳克/毫升)，服用0.9毫克含片后19分钟为(8.88±5.89纳克/毫升)。剂量-暴露关系表明，未观察到明显偏离剂量比例性，表明药代动力学呈线性。为了进一步了解十二碳-2E,4E,8Z,10E/Z-四烯酸异丁酰胺的药代动力学，应用混合效应建模程序建立了房室群体药代动力学模型。结果表明，在所研究的剂量范围内，十二碳-2E,4E,8Z,10E/Z-四烯酸异丁酰胺的药代动力学呈线性，吸收非常迅速（t(1/2)=6分钟），显然没有滞后时间，因此表明药物有一部分可能通过口腔黏膜吸收。
