Wang Yi-Han, Hong Yan-Long, Feng Yi, Xu De-Sheng, Liang Shuang, Lin Xiao, Shen Lan
Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Room 5117, No. 1200 Cailun Road, Shanghai, 201203, People's Republic of China.
Eur J Drug Metab Pharmacokinet. 2012 Jun;37(2):91-7. doi: 10.1007/s13318-011-0073-6. Epub 2012 Feb 10.
Senkyunolide I is an active ingredient of Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. In the present paper, we describe the isolation and elucidation of senkyunolide I from the ethanol extract of Rhizoma Chuanxiong and its pharmacokinetic behavior after intravenous and oral administration to normal and migrainous rats. After intravenous administration, senkyunolide I was rapidly distributed (V ( z )/F 2.07 ± 0.43 L/kg) and eliminated from the plasma (CL( z ) 2.56 ± 0.29 L/h/kg and t (1/2z ) 0.56 ± 0.13 h). After administration orally to normal rats at two dosages (20 and 72 mg/kg), the pharmacokinetic parameters of senkyunolide I were as follows: T (max) 0.25 ± 0.06 and 0.38 ± 0.11 h, C (max) 5,236.3 ± 802.8 and 22,071.9 ± 3,456.1 mg/L, Area under the curve(AUC)((0-t)) 5,217.5 ± 1,029.5 and 21,480.2 ± 3,003.1 μg h/L, respectively. Its oral absolute bioavailability at the two dosages was 67.2 and 76.9%, respectively. Intriguingly, migraine caused some significant changes in its pharmacokinetic parameter. For example, when compared with its pharmacokinetic behavior in normal rats at the two dosages, on average, its clearance decreased by 68% and volume of distribution increased by 342% in migrainous rats, both of which contributed to its several-fold increase in t (1/2z) and AUC. C (max) and AUC of senkyunolide I increased almost proportionally with dose between 20 and 72 mg/kg and the pharmacokinetics fit linear kinetic feature. The pharmacokinetic parameters of senkyunolide I were significantly different in normal and migrainous rats, which should be taken into account during the design of a clinical dosage regimen for senkyunolide I.
川芎内酯 I 是中药川芎的一种活性成分，川芎常用于治疗心血管疾病。在本文中，我们描述了从川芎乙醇提取物中分离和鉴定川芎内酯 I 的过程，以及其在正常大鼠和偏头痛大鼠静脉注射和口服给药后的药代动力学行为。静脉注射后，川芎内酯 I 迅速分布（V(z)/F 2.07±0.43 L/kg）并从血浆中消除（CL(z) 2.56±0.29 L/h/kg 和 t(1/2z) 0.56±0.13 h）。以两种剂量（20 和 72 mg/kg）给正常大鼠口服后，川芎内酯 I 的药代动力学参数如下：T(max) 分别为 0.25±0.06 和 0.38±0.11 h，C(max) 分别为 5236.3±802.8 和 22071.9±3456.1 mg/L，曲线下面积（AUC）((0 - t)) 分别为 5217.5±1029.5 和 21480.2±3003.1 μg h/L。两种剂量下其口服绝对生物利用度分别为 67.2%和 76.9%。有趣的是，偏头痛使其药代动力学参数发生了一些显著变化。例如，与两种剂量下正常大鼠的药代动力学行为相比，偏头痛大鼠中其清除率平均降低了 68%，分布容积增加了 342%，这两者都导致其 t(1/2z) 和 AUC 增加了几倍。在 20 至 72 mg/kg 之间，川芎内酯 I 的 C(max) 和 AUC 几乎与剂量成比例增加，且药代动力学符合线性动力学特征。川芎内酯 I 的药代动力学参数在正常大鼠和偏头痛大鼠中有显著差异，在设计川芎内酯 I 的临床给药方案时应予以考虑。
