Introduction: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases, including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration.

Methods: We developed a method based on ultra-high-performance liquid chromatographytandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague- Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples.

Results: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including C_max, T_max, T_1/2 and AUC_(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, T_max was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, C_max was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), T_max was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC_(0~t) was 1.93 ± 0.15 mg/mL.h in ARR and 1.70 ± 0.15 mg/mL.h in ARR-DG (P<0.05). For 6-shogaol, C_max was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), T_max was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T_1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC_(0~t) was 2.15 ± 0.18 mg/mL.h in DG and 2.73 ± 0.15 mg/mL.h in ARR-DG (P<0.01).

Conclusion: Pharmacokinetic interactions between ARR and DG decreased T_max, increased T_1/2 but did not affect the overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decreased C_max and T_max but increased T1/2 and AUC_(0~t) of 6-gingerol in DG. The interactions increased Cmax and AUC_(0~t) but decreased Tmax and T_1/2 of 6-shogaol in DG. Interactions in ARRDG did not affect the pharmacokinetics of sesamin.

简介： 细辛 (ARR) 和干姜 (Zingiber officinalis) (DG) 在中药制剂中经常一起用于治疗呼吸道疾病，包括感冒、支气管炎和肺炎。以前的研究表明 ARR 和/或 DG 可能会影响其他草药成分的药代动力学。在目前的研究中，我们检查了大鼠口服给药后 ARR 和 DG 之间的药代动力学相互作用。

方法：我们开发了一种基于超高效液相色谱串联质谱法的方法，可同时测量 ARR（L-asarinin 和芝麻素）和 DG（6-姜酚和 6-shogaol）中的两种活性成分的血清浓度。成年 Sprague-Dawley 大鼠饥饿过夜，然后通过胃管饲给予 ARR 提取物、DO 提取物或 ARR 和 DG 的共煎剂（每公斤体重 6 克原料；每组 n = 6）。在给药之前和之后的以下时间 (h) 采集血样：0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0 和 24.0。使用独立样品的Student's t检验比较药代动力学参数。

结果：已开发出一种简单、快速、灵敏的分析方法，可同时检测 ARR-DG 草药对中的四种生物活性成分。使用非房室模型和DAS 2.0药代动力学软件计算药代动力学参数，包括C _max、T _max、T _1/2和AUC _(0~t)。对于 L-asarinin，ARR 动物的T _max为 2.00 ± 0.00 小时，ARR-DG 动物的T _max为 1.67±0.26 小时（P<0.05），ARR 中的 T1/2 为 8.58 ± 1.75 小时，ARR-DG 中的 T 为 11.93 ± 2.13 小时(P<0.05)。对于 6-姜酚，DG 动物中的C _max为 350.48 ± 23.85 ng/mL，ARR-DG 中的C _max为 300.21 ± 20.02 ng/mL（P<0.01），T _max在 DG 中为 2.83 ± 0.41 小时，在 ARR 中为 2.17 ± 0.41 小时-DG (P<0.05) 和 AUC_(0~t)在 ARR 中为 1.93 ± 0.15 mg/mL.h，在 ARR-DG 中为 1.70 ± 0.15 mg/mL.h (P<0.05)。对于 6-shogaol，DG 动物中的C _max为 390.28 ± 26.02 ng/mL，ARR-DG 中的C _max为 455.63 ± 31.01 ng/mL（P<0.01），T _max在 DG 中为 2.93 ± 0.10 h，在 ARR 中为 1.92 ± 0.10 ng/mL -DG (P<0.01)，T _1/2在 DG 中为 3.74 ± 0.29 h，在 ARR-DG 中为 3.28 ± 0.22 h (P<0.01)，AUC _(0~t)为 2.15 ± 0.18 mg/mL.h在 DG 和 2.73 ± 0.15 mg/mL.h 在 ARR-DG (P<0.01)。

结论：ARR 和 DG 之间的药代动力学相互作用降低了 T _max，增加了 T _1/2但不影响 ARR 中 L-asarin 的整体生物利用度。ARR-DG 中的相互作用降低了 C _max和 T _max但增加了 DG 中 6-姜酚的T1/2 和 AUC _(0~t)。相互作用增加了 Cmax 和 AUC _(0~t)，但降低了 DG 中 6-shogaol 的Tmax 和 T _1/2。ARRDG 中的相互作用不影响芝麻素的药代动力学。