Aldara Mechanism of Action

Pharmacology: Pharmacodynamics: Imiquimod is an immune response modifier. It has no direct antiviral activity in cell culture. A mechanism of action study in 22 patients with genital/perianal warts shows that imiquimod induces cytokines including interferon-α at the treatment site. In addition, HPV E7 and L1 mRNA as well as HPV DNA are significantly decreased following treatment. However, the clinical relevance of these findings is unknown.
Clinical Studies: In a double-blind, placebo-controlled clinical trial, Aldara applied 3 times a week for treatment of genital and perianal warts had wart clearance that were statistically significantly greater than the placebo control. The percentage of patients achieving total clearance was 77% for females and 40% for males. The percentage of patients achieving partial wart area (>50%) reduction was 91% for females and 74% for males. The median baseline wart area was 69 mm² (range 8-5225 mm²). Visible wart changes occurred as early as 4 weeks and some patients required 16 weeks. The median time to total wart clearance was 10 weeks. In another study, Aldara applied daily, 59% of the males and 84% of the females achieved total clearance of their genital/perianal warts. A low percentage (6-23%) of the patients who achieved total clearance of their warts experienced a recurrence of their warts during the 12-week follow-up period. In 2 studies, some patients achieved total clearance or additional reduction in wart area during a 4-week treatment-free observation period following Aldara treatment. Thus, some patients with wart tissue remaining after Aldara treatment may continue to show clearing of their warts.
Pharmacokinetics: Less than 0.9% of a topically applied single dose of radiolabelled imiquimod was absorbed through the skin of human subjects. The small amount of imiquimod which was absorbed into the systemic circulation was promptly excreted by both urinary and faecal routes at a mean ratio of approximately 3:1. No quantifiable levels (>5 ng/mL) of imiquimod were detected in serum after single or multiple topical doses. The data defining systemic absorption of imiquimod are limited by the use of bioanalytical method with a 5 ng/mL lower limit or quantitation. Systemic exposure (percutaneous penetration) was calculated from the recovery of carbon-14 (¹⁴C) imiquimod in urine and faeces.