Mills Paul C, Magnusson Beatrice M, Cross Sheree E
School of Veterinary Science, University of Queensland, Brisbane, Qld. 4072, Australia.
Vet J. 2006 Mar;171(2):276-80. doi: 10.1016/j.tvjl.2004.11.013. Epub 2005 Jan 19.
The effects of the vehicles phosphate-buffered saline (PBS), ethanol (EtOH; 50% in PBS w/w) and propylene glycol (PG; 50% in PBS w/w) and the region of administration on in vitro transdermal penetration of testosterone was investigated in the dog. Skin was harvested from the thorax, neck (dorsal part) and groin regions of greyhounds after euthanasia and stored at -20 degrees C until required. The skin was then de-frosted and placed into Franz-type diffusion cells which were maintained at approximately 32 degrees C by a water-bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled (14C) testosterone, in each vehicle were applied to the outer (stratum corneum) surface of each skin sample and aliquots of receptor fluid were collected at 0, 2, 4, 8, 16, 20, 22 and 24h and analysed for testosterone by scintillation counting. The maximum flux (J(max)) of testosterone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH or 50% PG, compared to PBS. In contrast, higher residues of testosterone were found remaining within the skin when PBS was used as a vehicle. This study shows that variability in percutaneous penetration of testosterone could be expected with formulation design and site of application.
在犬类动物中，研究了赋形剂磷酸盐缓冲盐水（PBS）、乙醇（EtOH；50%于PBS中，重量/重量）和丙二醇（PG；50%于PBS中，重量/重量）以及给药部位对睾酮体外透皮渗透的影响。安乐死后，从灵缇犬的胸部、颈部（背部）和腹股沟区域采集皮肤，并储存在-20℃直至需要使用。然后将皮肤解冻并放入Franz型扩散池中，通过水浴将其维持在约32℃。将含有痕量放射性标记（14C）睾酮的睾酮饱和溶液分别施加到每个皮肤样品的外表面（角质层），并在0、2、4、8、16、20、22和24小时收集受体液等分试样，通过闪烁计数分析睾酮含量。与PBS相比，当睾酮溶解在含有50%EtOH或50%PG的赋形剂中时，所有部位的睾酮最大通量（J(max)）均显著更高。相反，当使用PBS作为赋形剂时，发现皮肤内残留的睾酮含量更高。本研究表明，睾酮经皮渗透的变异性可能与制剂设计和应用部位有关。
