Department of Chinese Pharmaceutics, School of Chinese Materia Medica, Eastern Campus, Beijing University of Chinese Medicine, Beijing 100102, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Feb 1;915-916:8-12. doi: 10.1016/j.jchromb.2012.12.011. Epub 2012 Dec 25.
Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae, respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic (i.g.)/intravenous (i.v.) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101-101 μg/mL for Gas and 0.0500-5.98 μg/mL for Pur (r(2)>0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4±6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g./i.v. administration of Gas and Pur alone or combined with each other (i.g.: 40 mg/kg Gas, 400 mg/kg Pur; i.v.: 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C(18) column with a gradient mobile phase of ACN-H(2)O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C(max), T(max), T(1/2), MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral bioavailability of Pur in combined administration was 10.7 times as much as that of single administration, whilst 1.52 folds in Gas. These results indicate that co-administration of Gas and Pur is a promising combination to gain higher bioavailability and it is suggested that doctors pay more attention to the dosages of the two when simultaneously using both of them.
天麻素（Gas）和葛根素（Pur）分别是源自中药天麻和葛根的生物活性物质，它们在中医临床处方中经常一起使用。它们的注射液在临床上联合用于治疗一些心脑血管疾病，特别是椎基底动脉缺血引起的眩晕。本文通过灌胃（i.g.）/静脉（i.v.）给药研究了天麻素和葛根素在大鼠血浆中的药代动力学相互作用。建立了一种同时测定大鼠血浆中天麻素和葛根素的可靠 HPLC 方法，天麻素的线性范围为 0.101-101μg/mL，葛根素的线性范围为 0.0500-5.98μg/mL（r(2)>0.993）。天麻素和葛根素的定量下限（LLOQ）和检测限（LOD）分别为 0.101、0.0486μg/mL 和 0.05、0.0245μg/mL。日内和日间精密度均小于 12.0%，而准确度均在 96.4±6.00%范围内。该方法已成功应用于大鼠单独或联合灌胃（i.g.：40mg/kg 天麻素，400mg/kg 葛根素；i.v.：20mg/kg 天麻素，20mg/kg 葛根素）后分析物的药代动力学研究。从大鼠视网膜静脉丛采集预定时间点的血样，用甲醇沉淀含内标酪氨酸（IS）的血浆，然后在 C(18)柱上进行色谱分离，采用 ACN-H(2)O 为流动相，梯度洗脱，并用 0.05%磷酸作为修饰剂。联合给药的药代动力学特征与单独给药明显不同。单独或联合灌胃（i.g.）给予天麻素后，C(max)、T(max)、T(1/2)、MRT 分别为 21.7μg/mL、0.250h、2.81h、0.830h 和 18.4μg/mL、0.550h、0.970h、1.37h，分别为 0.490μg/mL、1.95h、1.33h、2.10h 和 2.01μg/mL、0.570h、4.00h、5.10h。联合给药时葛根素的相对口服生物利用度是单独给药时的 10.7 倍，而天麻素则是 1.52 倍。这些结果表明，天麻素和葛根素联合使用是一种提高生物利用度的有前途的组合，建议医生在同时使用这两种药物时，要注意它们的剂量。
