Abstract

Objective: The objective of this single-center, open-label trial was to evaluate the percutaneous penetration of Aldara™ (imiquimod) cream, 5% when applied topically to patients with anogenital warts using a more frequent/aggressive dosing regimen.

Methods: Ten otherwise healthy males and six otherwise healthy, nonpregnant, nonlactating females with histology results suggestive of, or diagnostic of, human papilloma virus/condyloma acuminata were enrolled. Females were required to be practicing an acceptable form of contraception control. Patients applied cream daily (8 ± 2 hours) until complete wart clearance, or for a maximum of 16 weeks. Following the initial dose, at approximately week 4, and at the end-of-treatment, patients were confined for 42 hours in order to obtain a series of blood and urine samples. These samples were analyzed for levels of imiquimod and two metabolites, S-26704 and S-27700. Biological marker levels were not included as a part of this trial.

Results: No quantifiable (≥5 ng/mL) levels of imiquimod or the two metabolites were observed in any of the serum samples collected. Five patients had quantifiable (≥10 ng/mL) imiquimod, S-26704, or both in urine. No quantifiable levels of S-27700 were observed. Complete clearance of warts occurred in 40% of male patients and 83% of female patients. Erythema was the most frequently observed local skin reaction and was moderate in intensity, although 6 of 16 patients reported a severe erythema reaction at some point in the study. Application site reactions (itching, burning and pain) were the most frequently reported adverse events.

Conclusion: The lack of quantifiable levels of imiquimod or metabolites in serum, together with sporadically occurring quantifiable but low levels in urine, indicate that systemic exposure, after daily application of Aldara cream to genital/perianal skin, may occur but is minimal; however, pharmacological (immune marker) effects were not evaluated because cytokine measurements were not obtained. A future trial assessing cytokine levels after topical Aldara therapy with minimal systemic levels of imiquimod would help assess systemic drug and pharmacological effects and utility of this product in pregnant women.