磷酸川芎嗪的鼻腔吸收及药动学研究

Study on Nasal Absorption and Pharmacokinetics of Ligustrazine Phosphate

目的研究磷酸川芎嗪的鼻黏膜吸收特性及体内药动学。方法采用大鼠在体鼻腔重循环法研究磷酸川芎嗪的体外吸收规律,计算吸收速率常数;采用固相萃取-高效液相色谱法测定大鼠血浆中药物浓度,计算药动学参数和生物利用度。结果一定范围内不同浓度药物的鼻黏膜吸收速率常数k无显著性差异;磷酸川芎嗪在大鼠体内的过程属于二室模型,溶液鼻腔给药的生物利用度为86.33%,凝胶剂鼻腔给药的生物利用度为77.25%。结论药物吸收呈一级动力学特征;磷酸川芎嗪鼻腔给药吸收迅速,生物利用度高。

OBJECTIVE To investigate the characteristics of nasal mucosa absorption of ligustrazine phosphate and its pharmacokinetics. METHODS In situ nasal recirculation method was used in experimental animal model to study the nasal absorption of ligustrazine phosphate in vitro, the rate constants of absorption were evaluated. The blood samples were collected from the rats and the plasma concentration was measured by SPE-HPLC. The pharmacokinetic parameters and absolute bioavailability were evaluated. RESULTS The rate constants of absorption had no significant difference among different concentrations of drug in certain ranges. The in vivo course in rats was fitted by the two-compartment model. The bioavailability of intranasal administration of solution and gel was 86.33% and 77.25%, respectively. CONCLUSION The nasal administration of ligustrazine phosphate can be absorbed rapidly and have a high bioavailability.