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目的:对磷酸川芎嗪的理化性质及生物学性质进行研究,为设计磷酸川芎嗪的不同剂型提供理论依据。方法:测定磷酸川芎嗪在不同温度及不同介质中的溶解度、表观油/水分配系数(P)、酸碱解离常数(pKa)、药物血浆蛋白结合率等体外理化性质及大鼠灌胃和静注磷酸川芎嗪水溶液后的药动学行为,以高效液相色谱法测定体外含量及血浆样品中磷酸川芎嗪的浓度。结果:磷酸川芎嗪属于易溶性药物;P值随pH升高呈S型变化;具有二级解离,pKa1=3.50,pKa2=6.86;血浆蛋白结合率为常数,大约为60%;在大鼠体内吸收快,代谢也快,绝对生物利用度较高。结论:磷酸川芎嗪在胃肠道吸收良好,溶解度高,基本属于生物药剂学分类系统(BCS)中I类药物,但在体内代谢迅速。
OBJECTIVE: To study the physicochemical properties and biological properties of ligustrazine phosphate to provide a theoretical basis for designing different dosage forms of ligustrazine phosphate. Methods: The physico-chemical properties of ligustrazine phosphate in different temperatures and different media, apparent physico-chemical properties such as oil / water partition coefficient (P), acid-base dissociation constant (pKa) And intravenous injection of tetramethylpyrazine phosphate aqueous solution after pharmacokinetic behavior, high performance liquid chromatography determination of in vitro levels and plasma samples of tetramethylpyrazine phosphate concentration. Results: Ligustrazine phosphate was a soluble drug; P value changed with the increase of pH, S type; with secondary dissociation, pKa1 = 3.50, pKa2 = 6.86; plasma protein binding rate was constant, Fast absorption in the body, metabolism is also fast, high absolute bioavailability. CONCLUSION: Tetramethylpyrazine phosphate is well absorbed in the gastrointestinal tract and has high solubility. It belongs to class I drug in the biological pharmacy classification system (BCS), but rapidly metabolized in vivo.