Yoshida Daisuke, Todo Hiroaki, Hasegawa Tetsuya, Sugibayashi Kenji
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Int J Pharm. 2007 Jun 7;337(1-2):142-7. doi: 10.1016/j.ijpharm.2006.12.040. Epub 2007 Jan 7.
Using advanced topical formulations containing potential chemical enhancer(s) or physical penetration-enhancing tools capable of delivering entrapped drug(s) directly into skin tissues with little influence of the stratum corneum barrier, local and systemic drug disposition may be markedly similar to direct injection into the skin and muscle. The objective of this study is to investigate the dermatopharmacokinetics and systemic drug disposition after topical application and topical injection. Salicylate (SA) disposition in the skin and muscle as administration sites, and in the systemic circulation were evaluated following intracutaneous (i.c.) injection of an isotonic solution of SA-Na (dose; 3.08 micromol). Subcutaneous (s.c.) and intramuscular (i.m.) injection were also evaluated for comparison. Dermatopharmacokinetics and systemic disposition of SA after i.c. and s.c. injections were analyzed using a 4-compartment model consisting of skin, muscle, and central and peripheral compartments, whereas SA disposition after i.m. injection was analyzed using a 3-compartment model consisting of muscle, and central and peripheral compartments. Moreover, the absorption rate constant of SA after i.c. injection (0.073 min(-1)) was slightly lower than that after s.c. injection (0.083 min(-1)), and much lower than that after i.m. injection (0.327 min(-1)). In addition, higher osmolarity and a larger volume of SA-Na injectant increased the retention of SA in the skin and decreased the absorption rate to the systemic circulation after i.c. injection. The effect of injection volume on SA disposition after i.c. injection was not so marked compared with that of osmotic pressure. These results are useful to design an injection-type topical delivery system.
使用含有潜在化学增强剂或物理渗透增强工具的先进局部用制剂，这些制剂能够将包裹的药物直接递送至皮肤组织，而对角质层屏障影响很小，局部和全身药物处置可能与直接注射到皮肤和肌肉中显著相似。本研究的目的是研究局部应用和局部注射后的皮肤药物动力学和全身药物处置情况。在皮内（i.c.）注射SA-Na等渗溶液（剂量；3.08微摩尔）后，评估了水杨酸（SA）在作为给药部位的皮肤和肌肉以及全身循环中的处置情况。还评估了皮下（s.c.）和肌肉内（i.m.）注射以作比较。i.c.和s.c.注射后SA的皮肤药物动力学和全身处置情况使用由皮肤、肌肉以及中央和外周隔室组成的四室模型进行分析，而i.m.注射后SA的处置情况使用由肌肉以及中央和外周隔室组成的三室模型进行分析。此外，i.c.注射后SA的吸收速率常数（0.073 min⁻¹）略低于s.c.注射后（0.083 min⁻¹），且远低于i.m.注射后（0.327 min⁻¹）。另外，较高的渗透压和较大体积的SA-Na注射剂增加了i.c.注射后SA在皮肤中的滞留，并降低了向全身循环的吸收速率。与渗透压相比，注射体积对i.c.注射后SA处置的影响不那么显著。这些结果有助于设计一种注射型局部给药系统。
