目的 考察吸波面积(AUAWC)法与HPLC法对川芎组分制剂在大鼠体内绝对生物利用度的同步测定方法, 确定AUAWC法用于组分中药生物利用度研究的可行性。方法 采用双周期自身交叉设计, 取60只SD大鼠分别iv川芎组分注射液和ig川芎组分片的同量药物混悬液, 给药后在不同时间点对大鼠进行取血, 分别采用AUAWC法与HPLC法测定大鼠血浆中2种川芎组分制剂的整体药物和阿魏酸钠、盐酸川芎嗪质量浓度, 用DAS 2.0软件计算药动学参数, 求其绝对生物利用度, 并比较2种方法获得的数据。结果 AUAWC法测得大鼠ig川芎组分片药液后整体药物的AUC_0-∞为(77.218±13.492)mg·min/L, 大鼠iv川芎组分注射液后整体药物的AUC_0-∞为(169.775±18.252)mg·min/L, 川芎组分片的绝对生物利用度为45.48%;HPLC法测得ig给药的阿魏酸钠和盐酸川芎嗪AUC_0-∞分别为(69.134±4.853)和(16.422±2.584)mg·min/L, iv给药的阿魏酸钠和盐酸川芎嗪的AUC_0-∞分别为(155.244±28.994)和(36.754±6.645)mg·min/L, 阿魏酸钠和盐酸川芎嗪的绝对生物利用度分别为44.53%和44.68%;2种方法测得的数值比较接近。结论 AUAWC法可用于川芎组分制剂中整体药物绝对生物利用度的测试, 其与HPLC法的结合解决了该制剂中整体和个体药物共同分析的问题, 也为复杂体系下复方、组分中药等混合药物生物利用度的研究提供了较好的启示作用。

Objective The absolute bioavailability of the preparation of Chuanxiong Radix components in rats was simultaneously studied by two methods of area under absorbance-wavelength curve (AUAWC) and high performance liquid chromatography (HPLC), which would confirm the feasibility that AUAWC could be used to determine the absolute bioavailability of components of Chinese materia medica (CMM). Methods Based on the random two-way cross-over design, 60 SD rats were given the injection of Chuanxiong Radix components by iv and the same amount of drug suspension of the tablet of Chuanxiong Radix components by ig, respectively. Blood samples were collected at various time points after the administration. Plasma concentration of the total components, sodium ferulate, and ligustrazine hydrochloride of the two preparations of Chuanxiong Radix components in rats was measured by AUAWC combined with HPLC. Pharmacokinetic parameters and absolute bioavailability were calculated by DAS 2.0 program and the data obtained by the two methods were compared. Results After ig administration, AUC_0-∞ of total components was (77.218 ± 13.492) mg·min/L by AUAWC and AUC_0-∞ of total component was (169.775 ± 18.252) mg·min/L for iv injection. The absolute bioavailability of tablet of ligustrazine hydrochloride were (69.134 ± 4.853) and (16.422 ± 2.584) mg·min/L, respectively by HPLC. As for iv injection, AUC_0-∞ of sodium ferulate and ligustrazine hydrochloride were (155.244 ± 28.994) and (36.754 ± 6.645) mg·min/L, respectively. The absolute bioavailabilities of ig administration were 44.53% and 44.68%, respectively. The data obtained by AUAWC were similar to by HPLC. Conclusion The method of AUAWC can be used to determine the absolute bioavailability on the mixed drugs in the tablet of Chuanxiong Radix components, which will be helpful to solve the problem that the total and individual drugs of the preparation can be coanalyzed together under the combination method of HPLC. It will provide better enlightenment to study the absolute bioavailability of the mixed drugs from Western compound chemicals or complex components in CMM.

福建省科技厅中药学重点实验室平台