Nishida K, Nakakoga Y, Sato N, Kawakami S, Mukai T, Sasaki H, Sakaeda T, Nakamura J
School of Pharmaceutical Sciences, Nagasaki University, Nagasaki, Japan.
Eur J Pharm Biopharm. 2000 Nov;50(3):397-402. doi: 10.1016/s0939-6411(00)00112-0.
The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use.
本研究的目的是获取可用于改善药物在肝脏表面的控释和驻留时间的信息。我们使用羧甲基纤维素钠盐(CMC-Na)和聚乙烯醇(PVA),以酚红作为模型,研究了粘性制剂对其吸收的影响。使用圆柱形玻璃池将酚红应用于大鼠肝脏表面后,在存在3% CMC-Na或15% PVA的情况下,酚红的最大血浆浓度降低。根据玻璃池中剩余酚红量计算的6小时吸收比率,在存在1%或3% CMC-Na和15% PVA时分别为68.6%、60.5%和48.7%(对照:73.1%)。由于吸收比率降低,添加粘性添加剂后6小时内排泄到胆汁和尿液中的酚红量减少。通过对血浆浓度曲线进行药代动力学分析来表征吸收速率的降低。粘性添加剂之间的吸收速率变化有所不同,这反映了体外释放实验的结果。因此,粘性添加剂可改变肝脏表面药物吸收速率的可能性被认为具有良好的治疗应用前景。