Hui X, Anigbogu A, Singh P, Xiong G, Poblete N, Liu P, Maibach H I
Department of Dermatology, University of California San Francisco, Surge 110, Box 0989, San Francisco, CA 94143-0989, USA.
J Pharm Sci. 2001 Sep;90(9):1269-76. doi: 10.1002/jps.1079.
The systemic pharmacokinetics and local drug distribution of sodium diclofenac in skin and underlying tissues was studied. Iontophoresis facilitated local and systemic delivery of diclofenac sodium compared with passive diffusion. The maximum plasma concentration of sodium diclofenac was achieved within 1 h of iontophoresis, and the delivery was proportional to applied current density (371 +/- 141 and 132 +/- 62 microg/L at 0.5 and 0.2 mA/cm(2), respectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.15 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutaneous tissue, and muscle beneath the drug application site (cathode) were significantly greater than plasma concentrations and concentrations of drug in similar tissues at the untreated sites. The results thus suggest that the cutaneous microvasculature is not always a perfect "sink" and that transdermal iontophoresis facilitated the direct penetration of diclofenac sodium to deeper tissues. No skin irritation was observed up to 0.5 mA/cm(2) current density and 7 mg/mL sodium diclofenac concentration.
研究了双氯芬酸钠在皮肤及皮下组织中的全身药代动力学和局部药物分布。与被动扩散相比，离子导入促进了双氯芬酸钠的局部和全身递送。离子导入1小时内达到双氯芬酸钠的最大血浆浓度，且递送量与施加的电流密度成正比（在0.5和0.2 mA/cm²时分别为371±141和132±62 μg/L）。双氯芬酸在兔体内的递送效率为0.15 mg/mA·h。药物应用部位（阴极）下方皮肤、皮下组织和肌肉中双氯芬酸钠的浓度显著高于血浆浓度以及未处理部位相似组织中的药物浓度。因此，结果表明皮肤微血管系统并不总是一个完美的“汇”，且经皮离子导入促进了双氯芬酸钠直接渗透至更深层组织。在电流密度达0.5 mA/cm²和双氯芬酸钠浓度达7 mg/mL时未观察到皮肤刺激。
