Mills Paul C, Cross Sheree E
School of Veterinary Science, University of Queensland, Brisbane, Queensland 4072, Australia.
Can J Vet Res. 2006 Oct;70(4):317-20.
An increasing number of formulations are applied to equine skin, yet variable penetration can affect efficacy, or the incidence of adverse effects, or both. To investigate the effects of common methods of skin preparation on transdermal drug penetration in vitro, we clipped, harvested, and froze skin samples from 5 Thoroughbred geldings. Thawed samples were prepared as follows: control (no preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with the use of adhesive tape. The samples were then placed in diffusion cells, and 2 g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin samples was measured over 10 h. Compared with control skin, significantly more MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A significantly higher rate of penetration and shorter lag time were also noted for MeSa with all the prepared skin samples, compared with the control samples. The results show that clinical techniques routinely used to clean or prepare skin can significantly affect the rate and extent of penetration of a topically applied drug. This may result in greater systemic availability of active drug, which could lead to enhanced efficacy and, possibly, a higher incidence of adverse effects.
越来越多的制剂被应用于马的皮肤,但不同的透皮情况会影响疗效、不良反应发生率或两者。为了研究常用皮肤预处理方法对体外透皮药物渗透的影响,我们从5匹纯种阉割公马身上采集、收获并冷冻皮肤样本。解冻后的样本制备如下:对照组(未预处理);用洗必泰水溶液(Aq-C,0.1% w/v)清洁;用洗必泰酒精溶液(Al-C,0.5% w/v)清洁;剃毛(Sh);或用胶带进行胶带剥离(Ta)。然后将样本置于扩散池中,并在角质层一侧涂抹2 g水杨酸甲酯(MeSa)凝胶(Dencorub)。在10小时内测量MeSa及其分析物水杨酸(Sa)透过皮肤样本的渗透情况。与对照皮肤相比,透过用Al-C或Sh预处理的皮肤(P < 0.01)、或用Aq-C或Ta预处理的皮肤(P < 0.05)渗透的MeSa显著更多,并且从用Aq-C、Al-C或Sh预处理的皮肤(P < 0.05)或用Ta预处理的皮肤(P < 0.01)在接受相回收的Sa显著更多。与对照样本相比,所有预处理皮肤样本的MeSa渗透速率也显著更高,滞后时间更短。结果表明,临床常规用于清洁或预处理皮肤的技术可显著影响局部应用药物的渗透速率和程度。这可能导致活性药物有更高的全身可用性,并可能提高疗效,以及可能增加不良反应的发生率。