附子复方治疗寒湿痹阻型痹证患者的安全性研究

Safety of compound formula of fuzi for the treatment of arthralgia with cold-damp obstruction type

目的研究附子复方治疗寒湿痹阻型痹证的安全性,为临床安全使用附子及其复方提供参考。方法按照中医证候积分不同,对56例受试者分别给予含不同剂量附子的中药复方水煎液口服,既定时间点采血并制备含药血浆样本,测取各样本药代动力学参数,并进行安全性分析。结果药动学仅检测出单酯型的苯甲酰乌头原碱(BAC)、苯甲酰新乌头原碱(BMA)、苯甲酰次乌头原碱(BHA)和双酯型的次乌头碱(HA),4种生物碱血药浓度均低于附子中毒剂量,药动学参数拟合最佳房室模型为二室模型,有别于动物实验结果。临床观察无明显不良事件发生。结论本研究所用附子各剂量的临床用药安全;各生物碱在人体内代谢差异较大,其代谢过程可能与其它未知因素有关。

Objective To explore the safety of compound formula of fuzi for the treatment of arthralgia with cold-damp obstruction type, so as to provide references for its safe clinical application. Methods According to different TCM syndrome scores, 56 cases were treated with TCM water decoction with different doses of fuzi. At predetermined time points, blood was collected to prepare the blood samples. Pharmacokinetic parameters in each sample were test to perform safety analysis. Results Only monoester-type Benzoylaconine （ BAC）, Benzoylmesaconine （ BMA）, Benzoylhypacoitine （BHA） and diesters-type hypaconitine （HA） were tested positive, which all had lower blood concentration than poison dosage of fuzi. The two compartment model was the best compartment model to fit the pharmacokinetic parameters, which was different from the results of animal experiment. Conclusion The dosages used in this study are safe in clinic; the differences of each alkaloid metabolism are significant, which may be associated with other unknown factors.