Yoshida Daisuke, Todo Hiroaki, Hasegawa Tetsuya, Sugibayashi Kenji
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Eur J Pharm Sci. 2008 Sep 2;35(1-2):5-11. doi: 10.1016/j.ejps.2008.04.003. Epub 2008 Apr 22.
The aim of this study was to investigate the effect of molecular weight on the topical migration and systemic absorption of drugs, sodium salicylate (SA), calcein sodium (CAL) and FITC-dextrans (FD-4, FD-10, FD-20 and FD-40), after intracutaneous (i.c.) injection. The apparent diffusion coefficients in the skin (D(s)) of SA, CAL and FD-4 after i.c. injection were almost the same and slightly less than 1x10(-4)cm(2)/min. The D(s) value drastically decreased with molecular weight more than 10kDa. The plasma concentration-time curve after i.c. injection was predicted by the convolution method. The ratio of AUC (observed/predicted) was approximately unity for SA, CAL and FD-4 although the systemic absorption of only FD-4 was delayed. In contrast, the AUC ratios of FD-10, FD-20 and FD-40 were about 0.5, 0.2 and 0.06, respectively, and obviously decreased with the molecular weight. The elimination of FD-10, FD-20 and FD-40 from the skin was slow and the drugs tended to remain in the muscle. These results indicated the importance of diffusion in the skin and permeability through the blood vessels for local migration and systemic absorption of drugs after penetration into viable skin.
本研究的目的是调查分子量对皮内注射后药物（水杨酸钠（SA）、荧光素钠（CAL）和异硫氰酸荧光素标记葡聚糖（FD-4、FD-10、FD-20和FD-40））局部迁移和全身吸收的影响。皮内注射后SA、CAL和FD-4在皮肤中的表观扩散系数（D(s)）几乎相同，略小于1×10(-4)cm(2)/min。当分子量超过10kDa时，D(s)值急剧下降。皮内注射后的血浆浓度-时间曲线通过卷积法预测。SA、CAL和FD-4的AUC（观察值/预测值）比值约为1，尽管只有FD-4的全身吸收有所延迟。相比之下，FD-10、FD-20和FD-40的AUC比值分别约为0.5、0.2和0.06，且明显随分子量降低。FD-10、FD-20和FD-40从皮肤中的消除缓慢，药物倾向于滞留在肌肉中。这些结果表明，扩散在皮肤中的重要性以及药物渗透进入活皮肤后通过血管的通透性对局部迁移和全身吸收的重要性。
