关键词: 萘哌地尔, 生物粘附, 药物动力学, 生物利用度

Abstract: To improve the bioavailability of naftopidil, bioadhesive sustained-release capsules and non-bioadhesive capsules were prepared. Bioadhesive polymers such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 (CP 934) were used in the bioadhesive capsules formulations. Naftopidil capsule and two formulations of bioadhesive sustained-release capsules (I and II) were respectively given to five healthy male dogs in an open randomized cross-over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method. The pharmacokinetic parameters and the relative bioavailability were measured. The AUC0→24, Cmax and Tmax of non-bioadhesive naftopidil capsules were 3494.7±466.47 h·ng·mL^-1, 697.48±94.22 ng·mL^-1 and 1.15±0.49 h. These pharmacokinetic parameters of bioadhesive sustained-release capsules I and II were 4618.46±316.68 h·ng·mL^-1 and 4746.44±317.22 h·ng·mL^-1, 468.59±61.25 ng·mL^-1 and 512.00±72.29 ng·mL^-1, both 4.0±0.71 h respectively. Results from statistical analysis showed that there were significant differences between the two bioadhesive formulations and the non-bioadhesive one in AUC0→24, Cmax and Tmax. The relative bioavailability of the two bioadhesive sustained-release capsules were respectively 133.40±12.72% and 137.53±17.49% when compared with non-bioadhesive capsules. The bioavailability of naftopidil in dogs was improved by using bioadhesion.

Key words: Naftopidil, Bioadhesion, Pharmacokinetics, Bioavailability