Jumbelic L C, Liebel F T, Southall M D
Preclinical Pharmacology, Skin Research Center, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ 08558, USA.
Skin Pharmacol Physiol. 2006;19(3):147-52. doi: 10.1159/000092595. Epub 2006 Apr 6.
Topical administration of chemicals such as methyl nicotinate that induce erythema have been employed to measure the effectiveness of formulations containing anti-inflammatory agents. Prior studies have utilized a single concentration of methyl nicotinate, between 36.5 and 100 mM, for all test subjects in evaluations of topical formulations. However, individuals have different thresholds of response to methyl nicotinate; thus, a single concentration may not be appropriate for all individuals and could result in the apparent lack of anti-inflammatory activity of the formulation being evaluated. In the current study, we evaluated the use of a minimal erythema concentration (MEC) of methyl nicotinate, defined as the lowest concentration that produces a complete and even erythema at the test site, compared with a 36.5-mM concentration of methyl nicotinate. Hydroalcoholic gels containing the nonsteroidal anti-inflammatory drug ibuprofen were compared with placebo. Diffuse reflectance spectroscopy was employed to measure differences in cutaneous inflammatory response between the control (placebo)-treated group and the ibuprofen-treated group. When chemical erythema was induced using an MEC of methyl nicotinate, greater reductions in erythema were seen in ibuprofen-treated sites compared with sites treated with a 36.5-mM concentration of methyl nicotinate. In conclusion, for an accurate assessment method of erythema induced by methyl nicotinate, consideration should be given to determining the extent of response of an erythema-producing agent on an individual basis. An MEC of methyl nicotinate should be determined and employed for each individual to obtain more consistent and reliable efficacy results of anti-inflammatory activity.
已采用局部施用如诱导红斑的烟酸甲酯等化学物质来测量含有抗炎剂的制剂的有效性。先前的研究在局部制剂评估中对所有测试对象都使用单一浓度的烟酸甲酯，介于36.5至100 mM之间。然而，个体对烟酸甲酯的反应阈值不同；因此，单一浓度可能不适用于所有个体，并且可能导致所评估制剂的抗炎活性明显缺乏。在本研究中，我们评估了使用烟酸甲酯的最小红斑浓度（MEC），定义为在测试部位产生完全且均匀红斑的最低浓度，并与36.5 mM浓度的烟酸甲酯进行比较。将含有非甾体抗炎药布洛芬的水醇凝胶与安慰剂进行比较。采用漫反射光谱法测量对照组（安慰剂）治疗组和布洛芬治疗组之间皮肤炎症反应的差异。当使用烟酸甲酯的MEC诱导化学性红斑时，与用36.5 mM浓度的烟酸甲酯治疗的部位相比，在布洛芬治疗的部位观察到红斑有更大程度的减轻。总之，对于烟酸甲酯诱导红斑的准确评估方法，应考虑根据个体情况确定产生红斑的药物的反应程度。应确定并为每个个体采用烟酸甲酯的MEC，以获得更一致和可靠的抗炎活性疗效结果。
