The naturally occurring betulinic acid (BA) and its derivative NVX‐207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX‐207 in equine skin and assess the compounds’ local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX‐207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven‐day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high‐performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX‐207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX‐207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors.

中文翻译：

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八匹健康马中局部应用桦木酸和 NVX-207 的浓度分布和安全性 - 一项随机、盲法、安慰剂对照、交叉试验研究。

天然存在的桦木酸 (BA) 及其衍生物 NVX-207 对马恶性黑色素瘤 (EMM) 细胞具有抗癌作用，并在体外对分离的马皮肤具有有效渗透作用。该研究的目的是确定 BA 和 NVX-207 在马皮肤中的体内浓度分布，并评估化合物的局部和全身耐受性，旨在开发针对 EMM 的局部治疗。八匹马在交叉设计中接受了 1% BA、1% NVX-207 或安慰剂的经皮治疗，每天两次，连续 7 天，每种制剂之间有 7 天的清除期。马在颈部和尾巴下方接受治疗。通过宫颈皮肤中的高效液相色谱法评估化合物的浓度分布。进行了临床和组织病理学检查以及血液分析。与 BA 相比，在皮肤中发现了更高浓度的 NVX-207。在所有三组中均观察到良好的全身耐受性和仅轻微的局部不良反应。该研究证实了 BA 和 NVX-207 在对患有 EMM 的马的进一步临床试验中的局部应用；然而，化合物在受肿瘤影响的皮肤中的渗透和渗透可能会发生改变。