玳玳黄酮自微乳化微丸在大鼠体内的生物利用度研究

Bioavailability of Self-Microemulsifying Pellets of Daidai Flavones in Rats

目的建立HPLC同时测定大鼠血浆中柚皮苷和新橙皮苷含量的方法,研究玳玳黄酮自微乳化微丸在大鼠体内的药物动力学和相对生物利用度。方法将随机分组的大鼠分别灌胃给药玳玳黄酮自微乳化微丸液及玳玳黄酮有效部位混悬液,剂量120 mg·kg-1(按玳玳总黄酮含量计),分别于0.083,0.167,0.333,0.5,0.667,1,2、4、6、8、10、12和24 h取血。采用HPLC同时测定血浆样品中柚皮苷和新橙皮苷的浓度,运用DAS 3.0药动学程序计算药动学参数。结果比较口服玳玳黄酮自微乳化微丸及玳玳黄酮有效部位混悬液的药动学参数,柚皮苷AUC0-24分别为(17.710±6.588)和(9.139±1.982)mg.h.L-1,ρmax分别为(4.816±1.329)和(1.575±0.324)mg.L-1,tmax分别为(0.611±0.086)和(0.917±0.204)h,t1/2分别为(13.078±6.382)和(11.678±6.919)h,新橙皮苷AUC0-24分别为(18.094±4.892)和(10.961±2.276)mg.h.L-1,ρmax分别为(5.657±1.391)和(2.096±0.512)mg.L-1,tmax分别为(0.583±0.091)和(0.806±0.222)h,t1/2分别为(14.606±7.562)和(10.985±6.963)h。以玳玳黄酮有效部位混悬液为参比,玳玳黄酮自微乳化微丸中柚皮苷和新橙皮苷的相对生物利用度分别为193.78%和165.08%。结论玳玳黄酮研制成玳玳黄酮自微乳化微丸制剂能提高其口服生物利用度和改善其药剂学性质。

OBJECTIVE To develop an HPLC method for simultaneously determining the contents of naringin and neohespiridin in rat plasma,and to investigate the pharmacokinetics and relative bioavailability of self-microemulsifying pellets of daidai flavones in rats. METHODS The rats were divided into two groups randomly. They were administered orally suspension of daidai flavones effec- tive parts and its self-microemulsifying pellets, which both contained 120 mg·kg-1 of flavonoids. Blood samples were collected at 0. 083,0. 167,0. 333,0. 5,0. 667,1,2, 4, 6, 8, 10, 12 and 24 h and the concentrations of naringin and neohesperidin in rat plasma were simultaneously determined by HPLC. The pharmaeokinetic parameters were calculated by DAS 3.0 pharmacokinetie program. RESULTS The pharmacokintic parameters of naringin in the self-microemulsifying pellets of daidai flavones and the suspension were as follows ： AUC0-24 （ 17. 710 ± 6. 588 ） and （ 9. 139 ± 1. 982 ） mg · h · L - 1, Pmax （ 4. 816 ± 1. 329 ） and （ 1. 572 ± 0. 324 ） mg · L- 1, tmax （0. 611 ± 0. 086） and （ 1. 575 ± 0. 324 ） h, and t1/2 （ 13. 078 ± 6. 382 ） and （ 11. 678 ± 6. 919 ） h, respectively. And the pharmaeokintic parameters of neohesperidin were as follow ： AUC0-24 （ 18. 094 ± 4. 892 ） and （ 10. 961 ± 2. 276 ） mg · h · L-1 ,Pmax （ 5. 657 ± 1. 391 ） and （ 2. 096 ± 0. 512 ） mg · L -1, tmax （ 0. 583 ± 0. 091 ） and （ 0. 806 ± 0. 222 ） h, and t1/2 （ 14. 606 ± 7. 562 ） and （ 10. 985 ± 6. 963 ） h, respec- tively. The relative bioavailabilities of naringin and neohesperidin in the self-microemulsifying pellets of daidai flavones were 193.78% and 165.08% , respectively. CONCLUSION The bioavailability of daidai flavones is increased by making them into self-microemul- sifying pellets, and the biopharmaceutieal property of the flavones is improved.