The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),i...The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)administration.After i.n.,i.g.and i.v.administration of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals.The concentration of TMPP in the samples was analyzed by HPLC.The area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration.After i.n.administration,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between i.n.route and i.v.injection was 0.68,which was greater than that obtained after i.g.administration(0.43).The systemic bioavailability obtained with i.n.administration was greater than that obtained by the i.g.route(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral cortex.Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.展开更多
目的建立HPLC法测定磷酸川芎嗪纳米脂质体中磷酸川芎嗪的含量。方法色谱柱为phenomenex Luna C18（2）100A（4．6mm×250mm，5μm）柱，phenomenex保护柱；流动相为甲醇-水（3：2）；流速1．0ml/min;检测波长295nm；拄温为室温。结...目的建立HPLC法测定磷酸川芎嗪纳米脂质体中磷酸川芎嗪的含量。方法色谱柱为phenomenex Luna C18（2）100A（4．6mm×250mm，5μm）柱，phenomenex保护柱；流动相为甲醇-水（3：2）；流速1．0ml/min;检测波长295nm；拄温为室温。结果磷酸川芎嗪与辅料及溶剂峰分离良好，在0．408～40．8μg/ml浓度范围内线性关系良好（r=0．9999）。结论该方法简便易行，准确可靠，可用于磷酸川芎嗪纳米脂质体的含量测定。展开更多
基金The authors gratefully acknowledge the financial support by Department of Science and Technology,Guangdong,China(2010B03070009).
文摘The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)administration.After i.n.,i.g.and i.v.administration of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals.The concentration of TMPP in the samples was analyzed by HPLC.The area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration.After i.n.administration,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between i.n.route and i.v.injection was 0.68,which was greater than that obtained after i.g.administration(0.43).The systemic bioavailability obtained with i.n.administration was greater than that obtained by the i.g.route(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral cortex.Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.
文摘目的建立HPLC法测定磷酸川芎嗪纳米脂质体中磷酸川芎嗪的含量。方法色谱柱为phenomenex Luna C18（2）100A（4．6mm×250mm，5μm）柱，phenomenex保护柱；流动相为甲醇-水（3：2）；流速1．0ml/min;检测波长295nm；拄温为室温。结果磷酸川芎嗪与辅料及溶剂峰分离良好，在0．408～40．8μg/ml浓度范围内线性关系良好（r=0．9999）。结论该方法简便易行，准确可靠，可用于磷酸川芎嗪纳米脂质体的含量测定。
