[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

[Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats].

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.