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泊洛沙姆凝胶作为精氨酸加压素经皮离子电渗递送的载体:大鼠体内性能评价

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats.

作者信息

Nair Vinod, Panchagnula Ramesh

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, 160 062, Punjab, India.

出版信息

Pharmacol Res. 2003 Jun;47(6):555-62. doi: 10.1016/s1043-6618(03)00043-4.

Abstract

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.

摘要

本研究描述了精氨酸加压素(AVP)经皮离子电渗递送时的制剂配方以及药代动力学和药效学活性评估,AVP是一种具有抗利尿活性的九肽。泊洛沙姆407用于形成稳定的凝胶,该凝胶不会降低AVP的释放。凝胶的释放速率符合 Higuchi 动力学,表明主要释放机制是扩散。单独使用离子电渗法以及与化学增强剂联合使用,以增强AVP的经皮渗透。药代动力学和药效学研究结果均强调了离子电渗法实现的“快速起效”特点。药代动力学数据与药效学活性之间的相关性仅为定性关系。组织病理学研究表明,单独使用离子电渗法或化学增强剂引起的皮肤毒性,可通过将这两种技术串联使用来降低。

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