Bucko Alicia D, Jarratt Michael, Stough Dowling B, Kyhl Laerke, Villumsen John, Hall Anders
a Academic Dermatology Associates , Albuquerque , NM , USA.
b DermResearch, Inc. , Austin , TX , USA.
J Dermatolog Treat. 2018 Feb;29(1):74-79. doi: 10.1080/09546634.2017.1329506. Epub 2017 May 25.
Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol mebutate effectively treats AKs on areas up to 25 cm, but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions.
Phase I, multicenter, open-label, uncontrolled, non-randomized trial. Patients received ingenol mebutate gel for three consecutive days on approximately 250 cm of sun-damaged skin on the full face (0.027%), the scalp (0.027%), or arm (0.06%).
Of 61 patients, 10 (face =8; arm =2) had ingenol mebutate in whole blood at subnanomolar levels (0.235-0.462 nM). The assayed metabolites were below the lower limit of quantification. Local skin responses increased during Days 1-4 and declined thereafter, approaching baseline by Day 16. Most adverse events were pain/pruritus of mild or moderate intensity.
Subnanomolar systemic exposure to ingenol mebutate was measured after application of the gel to approximately 250 cm on the full face, scalp, or arm under maximum use conditions. No clinically relevant systemic adverse reactions were observed, and local skin responses were manageable.
光化性角化病（AK）与鳞状细胞癌处于疾病连续谱上，可在日光损伤皮肤的癌前病变区域以亚临床和临床可见病变的形式出现。 ingenol mebutate可有效治疗面积达25平方厘米的AK，但光化性角化病可累及更大面积的皮肤。本试验评估了ingenol mebutate凝胶在最大使用条件下用于更大面积皮肤时的全身暴露情况和安全性。
I期多中心、开放标签、非对照、非随机试验。患者连续三天在全脸（0.027%）、头皮（0.027%）或手臂（0.06%）约250平方厘米的日光损伤皮肤上涂抹ingenol mebutate凝胶。
61例患者中，10例（面部8例；手臂2例）全血中ingenol mebutate水平处于亚纳摩尔水平（0.235 - 0.462 nM）。检测到的代谢物低于定量下限。局部皮肤反应在第1 - 4天增加，此后下降，到第16天接近基线水平。大多数不良事件为轻度或中度的疼痛/瘙痒。
在最大使用条件下，在全脸、头皮或手臂约250平方厘米的皮肤上涂抹凝胶后，检测到ingenol mebutate的亚纳摩尔全身暴露。未观察到临床相关的全身不良反应，局部皮肤反应可控。
