[通过生物黏附提高犬体内萘哌地尔的生物利用度]

[Improving bioavailability of naftopidil by using bioadhesion in dogs].

作者信息

Ding J S, Jiang X H, Yuan M

机构信息

Second Affiliated Hospital of Hu'nan Medical University, Changsha 410011, China.

出版信息

Yao Xue Xue Bao. 2001 May;36(5):377-80.

PMID:12584863

Abstract

AIM

To prepare naftopidil bioadhesive sustained-release capsule and study their pharmacokinetics and relative bioavailability in the dog.

METHODS

Bioadhesive polymers such as hydroxypropyl methylcellulse (HPMC) and Carbopol 934 (CP 934) were used in capsule prescriptions. Naftopidil capsule and two formulations of bioadhesive sustained-release capsules (I and II) were given to five healthy male dogs in a cross-over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method and the pharmacokinetic parameters as well as the relative bioavailability were measured.

RESULTS

The C0-->infinity, Cmax and Tmax of naftopidil capsule was (3728 +/- 573) h.ng.mL-1, (697 +/- 94) ng.mL-1 and (1.2 +/- 0.5) h. These parameters of bioadhesive sustained-release capsule I and II, respectively, were (5518 +/- 391) h.ng.mL-1 and (5636 +/- 427) h.ng.mL-1; (468 +/- 61) ng.mL-1 and (512 +/- 72) ng.mL-1; both (4.0 +/- 0.7) h. Results from statistics showed that there were significant difference between bioadhesive formulations and the non-bioadhesive one in C0-->infinity, Cmax and Tmax. The bioadhesive formulations and the non-bioadhesive one were not bioequivalent, the relative bioavailability of the two bioadhesive sustained-release capsules were respectively 150% +/- 14% and 154% +/- 23% when compared with the non-bioadhesive capsule.

CONCLUSION

It is much improving bioavailability of naftopidil by using bioadhesion.

摘要

目的

制备萘哌地尔生物黏附性缓释胶囊，并研究其在犬体内的药代动力学及相对生物利用度。

方法

在胶囊处方中使用羟丙基甲基纤维素（HPMC）和卡波姆934（CP 934）等生物黏附性聚合物。采用交叉试验，将萘哌地尔胶囊及两种生物黏附性缓释胶囊制剂（Ⅰ和Ⅱ）给予5只健康雄性犬。采用新建立的高效液相色谱法测定血浆中萘哌地尔浓度，并计算药代动力学参数及相对生物利用度。

结果

萘哌地尔胶囊的C0→∞、Cmax和Tmax分别为（3728±573）h·ng·mL-1、（697±94）ng·mL-1和（1.2±0.5）h。生物黏附性缓释胶囊Ⅰ和Ⅱ的上述参数分别为（5518±391）h·ng·mL-1和（5636±427）h·ng·mL-1；（468±61）ng·mL-1和（512±72）ng·mL-1；均为（4.0±0.7）h。统计学结果显示，生物黏附性制剂与非生物黏附性制剂在C0→∞、Cmax和Tmax方面存在显著差异。生物黏附性制剂与非生物黏附性制剂不等效，两种生物黏附性缓释胶囊与非生物黏附性胶囊相比，相对生物利用度分别为150%±１4%和154%±23%。