Establishing a minimal erythema concentration of methyl nicotinate for optimum evaluation of anti-inflammatories.
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.
Jumbelic
L C
LC
Preclinical Pharmacology, Skin Research Center, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ 08558, USA.
Liebel
F T
FT
Southall
M D
MD
D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003877:Dermatitis, Contact / Q000188:drug therapy; D004890:Erythema / Q000139:chemically induced* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009539:Nicotinic Acids / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009539:Nicotinic Acids; C008473:methyl nicotinate; D007052:Ibuprofen