Pharmacokinetic behavior of argirein, derived from rhein, is characterized as slow release and prolonged T_1/2 of rhein in rats

详细信息	查看全文 | 推荐本文 |

• 作者：Xiao-Dong Cong^a ; ¹ ; Peng-Rong Fu^a ; ¹ ; De-Zai Dai^b ; ^{dezaidai@vip.sina.com} ; Yun Zhang^a ; Yin Dai^b
• 关键词：Argirein ; Rhein ; Pharmacokinetic ; Bioavailability ; HPLC ; Rat
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：15 August, 2012
• 卷：46
• 期：5
• 页码：468-474
• 文件大小：453 K

摘要

Aim

Rhein is an effective ingredient from Rheum palmatum L., Polygonum cuspidatum Sielb.et Zucc., Polygonum multiflorum Thunb. and has anti-inflammatory activity, however, plasma levels are too high and T_1/2 is not long enough following oral medication. Therefore, a modification of the rhein moiety was encouraged to improve the pharmacokinetic behavior. Argirein was produced by connecting rhein with l-arginine through hydrogen bond, which releases both rhein and l-arginine while getting into the body. The present study was to verify if the pharmacokinetic profile of argirein by measuring the released rhein is improved against those of untreated rhein administered alone.

Methods

A reversed-phase HPLC with a mobile phase of methanol mixed with acetate buffer was conducted. Rhein was monitored after arginine administration by i.g. and i.v. routes. Rhein alone was also administered and compared.

Results

The C_max and AUC_0-48 of the released rhein following argirein medication were less than those following rhein administered. The bioavailability of argirein was 18.5-20.8%against 22.77-25.22%of rhein. A delayed T_max, a reduced C_max and AUC_0-t and an increased T_1/2 were significant in the argirein group as compared with those in the rhein group.

Conclusion

The pharmacokinetic behavior of oral argirein presents a slow release property against those following oral rhein in rats. The released rhein following oral argirein is suitable in suppressing chronic inflammatory reactions attributed to prolonged T_1/2 and delayed T_max due to its slow release pharmacokinetic characteristics.