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马来酸噻吗洛尔的体外透皮离子电渗转运:年龄和物种的影响

In vitro transdermal iontophoretic transport of timolol maleate: effect of age and species.

作者信息

Kanikkannan N, Singh J, Ramarao P

机构信息

College of Pharmacy, Florida A & M University, Tallahassee, FL 32307, USA.

出版信息

J Control Release. 2001 Mar 12;71(1):99-105. doi: 10.1016/s0168-3659(01)00208-5.

Abstract

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. In the present study, the effect of biological parameters such as age of the animal and species variation (rat, rabbit, mouse, guinea pig and human) on the transdermal iontophoretic transport was studied using timolol maleate (TM) as a model drug. The iontophoretic transport of TM across the skins obtained from the rats of different age groups was found to be similar. The results of the present study suggest that the age of the animal (Wistar rats: 1-8 months) did not appear to influence the transdermal iontophoretic transport of TM significantly. The amount of TM transported during iontophoresis (2 h) was significantly different among the different skin species. But the total amount of TM transported up to 24 h (2 h iontophoresis+22 h post-iontophoretic passive diffusion) was not significantly different among the different species studied. The present study provides further evidence that iontophoresis technique reduces the interspecies differences in the transdermal permeation of drugs, which is normally observed in passive diffusion of drugs. However, it must be noted that excised skins have been used in the present study to investigate the role of age and species variation on the iontophoretic transport of TM. The influence of these parameters under in vivo conditions might be different considering the physiological differences in different species and in the animals of different age groups.

摘要

经皮离子导入法对于全身递送相对高分子量的水溶性和离子性药物(包括肽类)而言,可能是一种很有前景的方法。在本研究中,以马来酸噻吗洛尔(TM)作为模型药物,研究了诸如动物年龄和物种差异(大鼠、兔子、小鼠、豚鼠和人类)等生物学参数对经皮离子导入转运的影响。发现TM在不同年龄组大鼠的皮肤中的离子导入转运情况相似。本研究结果表明,动物年龄(Wistar大鼠:1 - 8个月)似乎并未显著影响TM的经皮离子导入转运。在离子导入过程中(2小时),不同皮肤物种间TM的转运量存在显著差异。但在长达24小时(2小时离子导入 + 22小时离子导入后被动扩散)内,不同研究物种间TM的总转运量并无显著差异。本研究进一步证明,离子导入技术减少了药物经皮渗透中的种间差异,而这种差异在药物被动扩散中通常会观察到。然而,必须注意的是,本研究中使用的是离体皮肤来研究年龄和物种差异对TM离子导入转运的作用。考虑到不同物种以及不同年龄组动物的生理差异,这些参数在体内条件下的影响可能会有所不同。

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